Insomnia and Osteoarthritis Study

• Sponsor: Johns Hopkins University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00374556
• Collaborator: (none)
• Enrollment: 30
• Location: 1
• Arms: 2
• Duration (Months): 95
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This research is being done to evaluate the effects of a sleeping pill (eszopiclone, Lunesta)in patients with arthritis of the knee who also suffer from chronic insomnia. This study will test whether Lunesta improves sleep, pain sensitivity, and daytime symptoms in patients with knee pain.

Condition or Disease	Intervention/Treatment	Phase
Osteoarthritis; Insomnia	Drug: Placebo; Drug: Eszopiclone	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: The Efficacy of Eszopiclone (Lunesta) for Chronic Insomnia Associated With Osteoarthritis.
• Study Start Date: Jan 1, 2006
• Actual Primary Completion Date: Dec 1, 2013
• Actual Study Completion Date: Dec 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Eszopiclone Eszopiclone 3mg capsules, once daily at bedtime for 12 weeks	Drug: Eszopiclone; 3mg capsule, once daily at bedtime
Placebo Comparator: Placebo 3mg placebo capsule, once daily at bedtime for 12 weeks	Drug: Placebo; 3mg placebo capsule, once daily at bedtime

Outcome Measures

Primary Outcome Measures

1. Wake After Sleep Onset (WASO) [Mean of baseline, 6 week follow-up, and 12 week follow-up]

   Total minutes of wakefulness recorded after sleep onset. (Recorded in Daily Sleep Diary) WASO= time awake in the middle of the night, not counting SL or time in bed after awakening. Recorded in minutes

2. Time in Bed [Mean of baseline, 6 week follow-up, and 12 week follow-up]

   Total time in bed, in minutes

3. Sleep Latency (SL) [Mean of baseline, 6 week follow-up, and 12 week follow-up]

   Sleep Latency: time taken to fall asleep, in minutes (as recorded in daily sleep diary)

4. Number of Awakenings [Mean of baseline, 6 week follow-up, and 12 week follow-up]

   As recorded in daily sleep diary

5. Total Sleep Time (TST) [Mean of baseline, 6 week follow-up, and 12 week follow-up]

   minutes spent asleep as recorded in daily sleep diary

6. Sleep Efficiency (SE) [Mean of baseline, 6 week follow-up, and 12 week follow-up]

   [(TST/ TIB)X 100], (%) as recorded in daily sleep diary

7. Sleep Quality (SQ) [Mean of baseline, 6 week follow-up, and 12 week follow-up]

   As recorded in daily sleep diary. Visual analog scales (VAS) Sleep Quality Ratings 0-100, 0= extremely poor sleep quality, (shallow and unrefreshing) and 100=excellent sleep quality (deep and refreshing)

8. WASO as Assessed by Actigraphy [Mean of baseline, 6 week follow-up, and 12 week follow-up]

   Subjects wore a Mini Mitter Actiwatch for two continuous weeks at each assessment periods to provide an objective index compared to the assessments made by daily sleep journal. Device is lightweight and worn on non-dominant wrist and contains and omni-directional accelerometer. The accelerometer records the occurrence and degree of motion with a minimal resultant force of .01g. Data are stored as activity counts within a specified epoch. WASO recorded by device = total minutes of wakefulness after sleep onset, in minutes.

9. TST as Assessed by Actigraphy [Mean of baseline, 6 week follow-up, and 12 week follow-up]

   Subjects wore a Mini Mitter Actiwatch for two continuous weeks at each assessment periods to provide an objective index compared to the assessments made by daily sleep journal. Device is lightweight and worn on non-dominant wrist and contains and omni-directional accelerometer. The accelerometer records the occurrence and degree of motion with a minimal resultant force of .01g. Data are stored as activity counts within a specified epoch. TST recorded by device = total minutes spent asleep

10. Sleep Efficiency as Assessed by Actigraphy [Mean of baseline, 6 week follow-up, and 12 week follow-up]

    Subjects wore a Mini Mitter Actiwatch for two continuous weeks at each assessment periods to provide an objective index compared to the assessments made by daily sleep journal. Device is lightweight and worn on non-dominant wrist and contains and omni-directional accelerometer. The accelerometer records the occurrence and degree of motion with a minimal resultant force of .01g. Data are stored as activity counts within a specified epoch. Sleep efficiency is the index of sleep percentage recorded, equal to total sleep time divided by the time in bed X 100 = X%.

11. Sleep Latency as Assessed by Actigraphy [Mean of baseline, 6 week follow-up, and 12 week follow-up]

    Subjects wore a Mini Mitter Actiwatch for two continuous weeks at each assessment periods to provide an objective index compared to the assessments made by daily sleep journal. Device is lightweight and worn on non-dominant wrist and contains and omni-directional accelerometer. The accelerometer records the occurrence and degree of motion with a minimal resultant force of .01g. Data are stored as activity counts within a specified epoch. Sleep latency is the time taken to fall asleep, or equal to lights out- sleep onset (sleep onset: time when sleep is first scored after lights out, first scorable epoch).

12. Insomnia Severity Index (ISI) Mean Total Scores [Mean of baseline, 6 week follow-up, and 12 week follow-up]

    The ISI is made up of 7 questions, each possible of earning a score of 0-4, making the total range 0-28, where 0 indicates no severity/no problem with sleep and therefore no insomnia, or 28, being very severe with the highest level of insomnia

13. Diffuse Noxious Inhibitory Control (DNIC) Index Scores [Mean of baseline, 6 week follow-up and 12 week follow-up]

    PPTh:a somedic algometer's 1cm2 rubber probe was placed over muscle belly, with pressure increasing steadily at constant rate (30kPA/Sec), until subject indicated that s/he "first felt pain." PPTh ratings were obtained on right brachioradialis & right trapezius in a random order (average was taken from both areas at each time point). During each cold pressor task, participants immersed contralateral hand (left) up to wrist, in a circulating cold water bath maintained at 4°C. 20 seconds after commencing hand immersion, PPTh was re-assessed on either right brachioradialis or right trapezius (the same site as baseline assessment). After PPTh assessment, participants removed hands from water. DNIC was measured as the % change in PPTh during cold pressor, relative to baseline PPTh [i.e., (mean PPTh during cold pressor / mean PPTh prior to cold pressor)*100]. Increase in PPTh during cold pressor (i.e., percentage scores above 100) reflects normal functioning of pain-inhibitory processes.

14. Temporal Summation (TS) [Mean of baseline, 6 week follow-up and 12 week follow-up at 46, 48, and 50 degrees C]

    TS :maximum windup pain rating - first windup pain rating (0-100). Contact heat stimuli at non tissue damaging temperatures were delivered using computer driven, peltier-element-based stimulator (Medoc, TSA II), with a 9 cm2 probe applied to left forearm. In order to assess temporal summation, three sequences of 10 heat pulses each (with stimulus temperatures of 46 degrees C, 48 degrees C, and 50 degrees C, in random order) were applied to left dorsal forearm. The thermode remains in fixed position during administration of 10 heat pulses that constitute a sequence. Within each sequence, successive thermal pulses at a given temperature are delivered for a duration of approximately 0.5 sec each, with a 2.5-sec inter-pulse interval. The rate of rise & fall of the thermode temp. is set at the device max .of 10 degrees C / S. Subjects verbally rate the perceived intensity of each thermal pulse on a 0-100 rating scale & may terminate the procedure at any time.100=max tolerable intensity

15. Mean Level of Pain Experienced Throughout the Day [Mean of baseline, 6 week follow-up and 12 week follow-up]

    Assessed using a Daily Pain Diary with a scale 0-100, 0 being no pain, 100 being the most severe/intense

16. Pain as Assessed by the Western Ontario and McMaster Universities Index of Osteoarthritis (WOMAC) Pain Severity Subscale [Mean of baseline, 6 week follow-up and 12 week follow-up]

    The WOMAC is a quality of scale life made up of three domains, pain, stiffness, and disability which each comprising of 5, 2, and 7 questions, respectively. A VAS was used for each subscale. Pain was assessed on a scale of 0-100, with 0 being absolutely no pain and 100 being maximum pain.

Secondary Outcome Measures

1. Heat Pain Threshold [Mean of baseline, 6 week follow-up and 12 week follow-up]

   Contact heat stimuli at non tissue damaging temperatures were delivered using computer driven, peltier-element-based stimulator (Medoc, TSA II), with a 9 cm2 probe applied to the left forearm. The thermode was affixed snugly via Velcro straps to ensure even skin contact and repositioned to an adjacent site after each trial to minimize sensitizationHPTh was assessed on the left ventral forearm using an ascending method of limits paradigm; from a non-painful 32°C baseline, the temperature was steadily increased at 0.5°C/sec. Two trials of heat pain threshold were conducted. Averages of both trials are presented from respective time point below. Subjects push a button when the stimulus "first feels painful" The temperature (degrees Celsius) at the time button is pushed is automatically recorded.

2. Heat Pain Tolerance (HPTOL) [Mean of baseline, 6 week follow-up and 12 week follow-up]

   Contact heat stimuli at non tissue damaging temperatures were delivered using computer driven, peltier-element-based stimulator (Medoc, TSA II), with a 9 cm2 probe applied to the left forearm. The thermode was affixed snugly via Velcro straps to ensure even skin contact and repositioned to an adjacent site after each trial to minimize sensitization. HPTOL was assessed on the left ventral forearm using an ascending method of limits paradigm; from a non-painful 32°C baseline, the temperature was steadily increased at 0.5°C/sec. Two trials of HPTOL were conducted. An average of both trials at each respective time point is presented below. Subjects push a button when the stimulus "becomes intolerable." The temperature (degrees Celsius) at the time button is pushed to terminate the stimulation is automatically recorded.

3. Pressure Pain Threshold [Mean of baseline, 6 week follow-up and 12 week follow-up]

   A Somedic algometer was used to assess pressure pain threshold (PPTh) similar to previous studies. The algometer's 1cm2 rubber probe was placed over the muscle belly, with the pressure increased steadily at a constant rate (30kPA/Sec), until the subject indicated that s/he "first felt pain." PPTh was assessed 2 times each, bilaterally, at (in a randomized order) the masseter muscle trapezius muscle, and at the proximal third of the brachioradialis muscle (forearm). The scores from each location were averaged for each participant at that respective time point. The same site was never stimulated consecutively. At least 90 s were maintained between successive stimuli

4. Quality of Life as Assessed by the Western Ontario and McMaster Universities Index of Osteoarthritis (WOMAC) Disability Subscale [Mean of baseline, 6 week follow-up and 12 week follow-up]

   The WOMAC is a quality of scale life made up of three domains, pain, stiffness, and disability which each comprising of 5, 2, and 7 questions, respectively. A VAS was used for each subscale. Disability was assessed on a VAS of 0-100, with 0 being absolutely no disability and 100 being maximum disability.

5. Quality of Life as Assessed by the Short Form-36 (SF-36) Physical Health Component Summary [Mean of baseline, 6 week follow-up and 12 week follow-up]

   The SF-36 is a broad, well normed measure of quality of life, comprised of 36 questions aggregated into 8 domains/dimensions. The Physical Component Summary was used here as a global index of physical health functioning. Scale 0-100, with 0 being worst functional level, 100 being the best.

6. Quality of Life as Assessed by the Short Form-36 (SF-36) Mental Health Component Summary [Mean of baseline, 6 week follow-up and 12 week follow-up]

   The SF-36 is a broad, well normed measure of quality of life, comprised of 36 questions aggregated into 8 domains/dimensions. The Mental Component Summary was used here as a global index of mental health functioning. Scale 0-100, with 0 being worst functional level, 100 being the best.

7. Joint Stiffness as Assessed by the Western Ontario and McMaster Universities Index of Osteoarthritis (WOMAC) Joint Stiffness Subscale [Mean of baseline, 6 week follow-up and 12 week follow-up]

   The WOMAC is a quality of scale life made up of three domains, pain, stiffness, and disability which each comprising of 5, 2, and 7 questions, respectively. A VAS was used for each subscale. Joint Stiffness was assessed on a VAS scale of 0-20, with 0 being no joint stiffness, and 20 being maximum stiffness.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 64 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age 18-64

• Diagnosed with and under physicians care for osteoarthritis of the knee according to American College of Rheumatology Criteria with radiographic evidence demonstrating at least grade 1 osteoarthritis (OA)

• Report at least typical arthritic pain>4 out of 10 (0=no pain, 10=the most extreme pain imaginable)

• Meet Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) and International Classification of Sleep Disorders, Revised definition (ICSD-R) criteria for either primary (psychophysiologic) insomnia or insomnia secondary to osteoarthritis

• Insomnia symptoms must include problems with middle of the night awakenings

• Insomnia symptom duration > 6 months

• Baseline, 2-week, sleep diary average wake after sleep onset time >30 minutes

• Baseline self-reported total sleep time < 6.5 hours per night

• Patients taking NSAID therapy for pain must be on a stable dose for a period of at least one month prior to initiating the study

Exclusion Criteria:

• Intrinsic sleep disorders other than insomnia (sleep apnea, periodic limb movement disorder, etc)

• Significant rheumatologic or chronic pain disorders other than osteoarthritis of the knee, including fibromyalgia or the complaint of widespread pain impacting 4 quadrants, complex regional pain syndrome, post herpetic neuralgia, etc)

• Major medical disease (including, hepatic impairment, chronic obstructive pulmonary disease/compromised respiratory function, cancer, dementia, diabetes, congestive heart failure, cerebrovascular disease, raynaud's syndrome)

• Active major psychiatric disorders (including dementia or cognitive impairment) and history of schizophrenia or bipolar I disorder

• History of serious suicide attempt; 6) history of alcohol or substance (including prescription medications) abuse

• Pregnancy or plans to become pregnant within 6 months

• Intraarticular steroid injection within the past month

• Regular (>3 days/week) use of antidepressants, antipsychotics, and mood stabilizers, within the past two months

• Regular (> 3/week) use of myorelaxants, narcotics, sedative hypnotics, and anticonvulsants within the past one month

• Unwilling or unable to discontinue all use of the medications listed in #10 for two weeks prior to starting the study

• Unwilling or unable to discontinue all centrally acting agents and all analgesic usage within 24 hours of pain testing sessions

• Refusal to provide consent to contact patient's physician to establish diagnosis and obtain medical record information

• Regular tobacco or nicotine use

• Heavy caffeine use [(>2 cups of coffee/day (equivalent)

• History of previous allergic reaction or severe side effects to sedative hypnotics

• Use of potent CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, troleandomycin, ritonavir, nelfinavir)

• In addition, subjects will undergo in-laboratory blood tests prior to receiving drug and will be excluded from further participation if they exhibit: a) positive pregnancy test, b) positive toxicology (benzodiazepine, opioids, Tetrahydrocannabinol (THC), alcohol, and stimulants), c) abnormal liver enzyme panel

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Johns Hopkins Hospital	Baltimore	Maryland	United States	21287

Sponsors and Collaborators

• Johns Hopkins University

Investigators

• Principal Investigator: Michael T. Smith, Ph.D., Johns Hopkins University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Johns Hopkins University
• ClinicalTrials.gov Identifier: NCT00374556
• Other Study ID Numbers: NA_00001703
• First Posted: Sep 11, 2006
• Last Update Posted: Mar 14, 2019
• Last Verified: Mar 1, 2019

• Keywords provided by Johns Hopkins University: eszopiclone; insomnia
• Additional relevant MeSH terms: Osteoarthritis; Sleep Initiation and Maintenance Disorders; Eszopiclone

Study Results

Participant Flow

Pre-assignment Detail	105 were assessed for eligibility. 75 were excluded based on not meeting inclusion criteria. 30 were randomized to one of 2 arms. One subject after randomization ( to placebo condition) was determined to be ineligible due to failing sleep apnea entry criteria. They were removed from the study and did not contribute to baseline data.

Arm/Group Title	Eszopiclone	Placebo
Arm/Group Description	Eszopiclone 3mg capsules, once daily at bedtime for 12 weeks Eszopiclone: 3mg capsule, once daily at bedtime	3mg placebo capsule, once daily at bedtime for 12 weeks Placebo: 3mg placebo capsule, once daily at bedtime
Period Title: Overall Study
STARTED	14	16
COMPLETED	13	15
NOT COMPLETED	1	1

Baseline Characteristics

Arm/Group Title	Eszopiclone	Placebo	Total
Arm/Group Description	Eszopiclone 3mg capsules, once daily at bedtime for 12 weeks Eszopiclone: 3mg capsule, once daily at bedtime	3mg placebo capsule, once daily at bedtime for 12 weeks Placebo: 3mg placebo capsule, once daily at bedtime	Total of all reporting groups
Overall Participants	14	15	29
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.64 (5.18)	52.93 (6.64)	53.76 (5.94)
Sex: Female, Male (Count of Participants)
Female	11 78.6%	8 53.3%	19 65.5%
Male	3 21.4%	7 46.7%	10 34.5%
Region of Enrollment (participants) [Number]
United States	14 100%	15 100%	29 100%
Kellgren Lawrence OA grade (units on a scale) [Mean (Standard Deviation) ]
Right knee	2.08 (0.86)	1.53 (0.91)	1.79 (0.92)
Left Knee	2.07 (1.07)	1.79 (1.05)	1.93 (1.05)
Kellgren Lawrence OA grade >=3 in either knee (participants) [Number]
Number [participants]	6 42.9%	4 26.7%	10 34.5%
BMI (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	29.41 (5.21)	31.36 (6.53)	30.42 (5.91)
Duration of OA (months) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [months]	87.7 (98.06)	108.5 (95.11)	95.6 (95.69)

Outcome Measures

1. Primary Outcome

Title	Wake After Sleep Onset (WASO)
Description	Total minutes of wakefulness recorded after sleep onset. (Recorded in Daily Sleep Diary) WASO= time awake in the middle of the night, not counting SL or time in bed after awakening. Recorded in minutes
Time Frame	Mean of baseline, 6 week follow-up, and 12 week follow-up

Outcome Measure Data

Analysis Population Description

Data was not included for all participants, as some were unable to complete the task or experienced technical difficulties.

Arm/Group Title	Placebo	Eszopiclone
Arm/Group Description	3mg placebo capsule, once daily at bedtime for 12 weeks Placebo: 3mg placebo capsule, once daily at bedtime	Eszopiclone 3mg capsules, once daily at bedtime for 12 weeks Eszopiclone: 3mg capsule, once daily at bedtime
Measure Participants	15	10
Baseline	117.33 (108.09)	88.0 (57.26)
6 week follow-up	81.00 (98.76)	65.56 (67.28)
12 week follow-up	61.94 (55.59)	58.57 (51.85)

2. Primary Outcome

Title	Time in Bed
Description	Total time in bed, in minutes
Time Frame	Mean of baseline, 6 week follow-up, and 12 week follow-up

Outcome Measure Data

Analysis Population Description

Data was not included for all participants, as some were unable to complete the task or experienced technical difficulties.

Arm/Group Title	Placebo	Eszopiclone
Arm/Group Description	3mg placebo capsule, once daily at bedtime for 12 weeks Placebo: 3mg placebo capsule, once daily at bedtime	Eszopiclone 3mg capsules, once daily at bedtime for 12 weeks Eszopiclone: 3mg capsule, once daily at bedtime
Measure Participants	15	10
Baseline	464.00 (134.31)	608.00 (243.48)
6 week follow-up	506.00 (120.22)	577.77 (130.26)
12 week follow-up	523.33 (128.55)	592.85 (113.39)

3. Primary Outcome

Title	Sleep Latency (SL)
Description	Sleep Latency: time taken to fall asleep, in minutes (as recorded in daily sleep diary)
Time Frame	Mean of baseline, 6 week follow-up, and 12 week follow-up

Outcome Measure Data

Analysis Population Description

Data was not included for all participants, as some were unable to complete the task or experienced technical difficulties.

Arm/Group Title	Placebo	Eszopiclone
Arm/Group Description	3mg placebo capsule, once daily at bedtime for 12 weeks Placebo: 3mg placebo capsule, once daily at bedtime	Eszopiclone 3mg capsules, once daily at bedtime for 12 weeks Eszopiclone: 3mg capsule, once daily at bedtime
Measure Participants	15	10
Baseline	58.33 (51.01)	47.50 (30.21)
6 week follow-up	45.00 (41.96)	33.33 (21.50)
12 week follow-up	31.38 (26.98)	41.42 (40.28)

4. Primary Outcome

Title	Number of Awakenings
Description	As recorded in daily sleep diary
Time Frame	Mean of baseline, 6 week follow-up, and 12 week follow-up

Outcome Measure Data

Analysis Population Description

Data was not included for all participants, as some were unable to complete the task or experienced technical difficulties.

Arm/Group Title	Placebo	Eszopiclone
Arm/Group Description	3mg placebo capsule, once daily at bedtime for 12 weeks Placebo: 3mg placebo capsule, once daily at bedtime	Eszopiclone 3mg capsules, once daily at bedtime for 12 weeks Eszopiclone: 3mg capsule, once daily at bedtime
Measure Participants	15	10
Baseline	3.53 (1.84)	3.70 (2.11)
6 week follow-up	3.06 (1.27)	3.11 (1.76)
12 week follow-up	2.38 (0.78)	3.42 (1.99)

5. Primary Outcome

Title	Total Sleep Time (TST)
Description	minutes spent asleep as recorded in daily sleep diary
Time Frame	Mean of baseline, 6 week follow-up, and 12 week follow-up

Outcome Measure Data

Analysis Population Description

Data was not included for all participants, as some were unable to complete the task or experienced technical difficulties.

Arm/Group Title	Placebo	Eszopiclone
Arm/Group Description	3mg placebo capsule, once daily at bedtime for 12 weeks Placebo: 3mg placebo capsule, once daily at bedtime	Eszopiclone 3mg capsules, once daily at bedtime for 12 weeks Eszopiclone: 3mg capsule, once daily at bedtime
Measure Participants	15	10
Baseline	255.66 (172.57)	370.50 (184.98)
6 week follow-up	339.33 (161.04)	454.44 (178.68)
12 week follow-up	409.44 (80.98)	437.14 (118.73)

6. Primary Outcome

Title	Sleep Efficiency (SE)
Description	[(TST/ TIB)X 100], (%) as recorded in daily sleep diary
Time Frame	Mean of baseline, 6 week follow-up, and 12 week follow-up

Outcome Measure Data

Analysis Population Description

Data was not included for all participants, as some were unable to complete the task or experienced technical difficulties.

Arm/Group Title	Placebo	Eszopiclone
Arm/Group Description	3mg placebo capsule, once daily at bedtime for 12 weeks Placebo: 3mg placebo capsule, once daily at bedtime	Eszopiclone 3mg capsules, once daily at bedtime for 12 weeks Eszopiclone: 3mg capsule, once daily at bedtime
Measure Participants	15	10
Baseline	55.54 (62.44)	62.44 (20.73)
6 week follow-up	66.31 (24.01)	77.48 (15.32)
12 week follow-up	80.07 (11.65)	75.06 (19.30)

7. Primary Outcome

Title	Sleep Quality (SQ)
Description	As recorded in daily sleep diary. Visual analog scales (VAS) Sleep Quality Ratings 0-100, 0= extremely poor sleep quality, (shallow and unrefreshing) and 100=excellent sleep quality (deep and refreshing)
Time Frame	Mean of baseline, 6 week follow-up, and 12 week follow-up

Outcome Measure Data

Analysis Population Description

Data was not included for all participants, as some were unable to complete the task or experienced technical difficulties.

Arm/Group Title	Placebo	Eszopiclone
Arm/Group Description	3mg placebo capsule, once daily at bedtime for 12 weeks Placebo: 3mg placebo capsule, once daily at bedtime	Eszopiclone 3mg capsules, once daily at bedtime for 12 weeks Eszopiclone: 3mg capsule, once daily at bedtime
Measure Participants	15	10
Baseline	44.40 (18.86)	37.90 (13.89)
6 week follow-up	52.46 (19.96)	55.33 (19.93)
12 week follow-up	59.16 (23.12)	55.71 (11.85)

8. Primary Outcome

Title	WASO as Assessed by Actigraphy
Description	Subjects wore a Mini Mitter Actiwatch for two continuous weeks at each assessment periods to provide an objective index compared to the assessments made by daily sleep journal. Device is lightweight and worn on non-dominant wrist and contains and omni-directional accelerometer. The accelerometer records the occurrence and degree of motion with a minimal resultant force of .01g. Data are stored as activity counts within a specified epoch. WASO recorded by device = total minutes of wakefulness after sleep onset, in minutes.
Time Frame	Mean of baseline, 6 week follow-up, and 12 week follow-up

Outcome Measure Data

Analysis Population Description

Data was not included for all participants, as some were unable to complete the task or experienced technical difficulties.

Arm/Group Title	Placebo	Eszopiclone
Arm/Group Description	3mg placebo capsule, once daily at bedtime for 12 weeks Placebo: 3mg placebo capsule, once daily at bedtime	Eszopiclone 3mg capsules, once daily at bedtime for 12 weeks Eszopiclone: 3mg capsule, once daily at bedtime
Measure Participants	14	12
Baseline	64.70 (39.14)	59.43 (15.81)
6 week follow-up	56.30 (25.34)	56.06 (250.80)
12 week follow-up	59.70 (39.18)	65.29 (17.99)

9. Primary Outcome

Title	TST as Assessed by Actigraphy
Description	Subjects wore a Mini Mitter Actiwatch for two continuous weeks at each assessment periods to provide an objective index compared to the assessments made by daily sleep journal. Device is lightweight and worn on non-dominant wrist and contains and omni-directional accelerometer. The accelerometer records the occurrence and degree of motion with a minimal resultant force of .01g. Data are stored as activity counts within a specified epoch. TST recorded by device = total minutes spent asleep
Time Frame	Mean of baseline, 6 week follow-up, and 12 week follow-up

Outcome Measure Data

Analysis Population Description

Data was not included for all participants, as some were unable to complete the task or experienced technical difficulties.

Arm/Group Title	Placebo	Eszopiclone
Arm/Group Description	3mg placebo capsule, once daily at bedtime for 12 weeks Placebo: 3mg placebo capsule, once daily at bedtime	Eszopiclone 3mg capsules, once daily at bedtime for 12 weeks Eszopiclone: 3mg capsule, once daily at bedtime
Measure Participants	14	12
Baseline	340.07 (71.23)	367.95 (79.73)
6 week follow-up	337.93 (75.00)	405.88 (79.29)
12 week follow-up	336.84 (87.63)	394.77 (96.86)

10. Primary Outcome

Title	Sleep Efficiency as Assessed by Actigraphy
Description	Subjects wore a Mini Mitter Actiwatch for two continuous weeks at each assessment periods to provide an objective index compared to the assessments made by daily sleep journal. Device is lightweight and worn on non-dominant wrist and contains and omni-directional accelerometer. The accelerometer records the occurrence and degree of motion with a minimal resultant force of .01g. Data are stored as activity counts within a specified epoch. Sleep efficiency is the index of sleep percentage recorded, equal to total sleep time divided by the time in bed X 100 = X%.
Time Frame	Mean of baseline, 6 week follow-up, and 12 week follow-up

Outcome Measure Data

Analysis Population Description

Data was not included for all participants, as some were unable to complete the task or experienced technical difficulties.

Arm/Group Title	Placebo	Eszopiclone
Arm/Group Description	3mg placebo capsule, once daily at bedtime for 12 weeks Placebo: 3mg placebo capsule, once daily at bedtime	Eszopiclone 3mg capsules, once daily at bedtime for 12 weeks Eszopiclone: 3mg capsule, once daily at bedtime
Measure Participants	14	12
Baseline	73.32 (12.34)	76.83 (8.74)
6 week follow-up	74.77 (8.87)	79.94 (7.49)
12 week follow-up	73.95 (14.15)	75.16 (7.58)

11. Primary Outcome

Title	Sleep Latency as Assessed by Actigraphy
Description	Subjects wore a Mini Mitter Actiwatch for two continuous weeks at each assessment periods to provide an objective index compared to the assessments made by daily sleep journal. Device is lightweight and worn on non-dominant wrist and contains and omni-directional accelerometer. The accelerometer records the occurrence and degree of motion with a minimal resultant force of .01g. Data are stored as activity counts within a specified epoch. Sleep latency is the time taken to fall asleep, or equal to lights out- sleep onset (sleep onset: time when sleep is first scored after lights out, first scorable epoch).
Time Frame	Mean of baseline, 6 week follow-up, and 12 week follow-up

Outcome Measure Data

Analysis Population Description

Data was not included for all participants, as some were unable to complete the task or experienced technical difficulties.

Arm/Group Title	Placebo	Eszopiclone
Arm/Group Description	3mg placebo capsule, once daily at bedtime for 12 weeks Placebo: 3mg placebo capsule, once daily at bedtime	Eszopiclone 3mg capsules, once daily at bedtime for 12 weeks Eszopiclone: 3mg capsule, once daily at bedtime
Measure Participants	14	12
Baseline	46.25 (58.44)	26.79 (24.73)
6 week follow-up	39.31 (48.31)	24.87 (17.06)
12 week follow-up	24.71 (27.42)	38.89 (23.49)

12. Primary Outcome

Title	Insomnia Severity Index (ISI) Mean Total Scores
Description	The ISI is made up of 7 questions, each possible of earning a score of 0-4, making the total range 0-28, where 0 indicates no severity/no problem with sleep and therefore no insomnia, or 28, being very severe with the highest level of insomnia
Time Frame	Mean of baseline, 6 week follow-up, and 12 week follow-up

Outcome Measure Data

Analysis Population Description

Data was not included for all participants, as some were unable to complete the task.

Arm/Group Title	Placebo	Eszopiclone
Arm/Group Description	3mg placebo capsule, once daily at bedtime for 12 weeks Placebo: 3mg placebo capsule, once daily at bedtime	Eszopiclone 3mg capsules, once daily at bedtime for 12 weeks Eszopiclone: 3mg capsule, once daily at bedtime
Measure Participants	14	14
Baseline	15.64 (6.02)	16.64 (4.98)
6 week follow-up	12.57 (4.65)	10.71 (6.38)
12 week follow-up	10.25 (5.19)	13 (6.33)

13. Primary Outcome

Title	Diffuse Noxious Inhibitory Control (DNIC) Index Scores
Description	PPTh:a somedic algometer's 1cm2 rubber probe was placed over muscle belly, with pressure increasing steadily at constant rate (30kPA/Sec), until subject indicated that s/he "first felt pain." PPTh ratings were obtained on right brachioradialis & right trapezius in a random order (average was taken from both areas at each time point). During each cold pressor task, participants immersed contralateral hand (left) up to wrist, in a circulating cold water bath maintained at 4°C. 20 seconds after commencing hand immersion, PPTh was re-assessed on either right brachioradialis or right trapezius (the same site as baseline assessment). After PPTh assessment, participants removed hands from water. DNIC was measured as the % change in PPTh during cold pressor, relative to baseline PPTh [i.e., (mean PPTh during cold pressor / mean PPTh prior to cold pressor)*100]. Increase in PPTh during cold pressor (i.e., percentage scores above 100) reflects normal functioning of pain-inhibitory processes.
Time Frame	Mean of baseline, 6 week follow-up and 12 week follow-up

Outcome Measure Data

Analysis Population Description

Data was not included for all participants, as some were unable to complete the task or experienced technical difficulties.

Arm/Group Title	Placebo	Eszopiclone
Arm/Group Description	3mg placebo capsule, once daily at bedtime for 12 weeks Placebo: 3mg placebo capsule, once daily at bedtime	Eszopiclone 3mg capsules, once daily at bedtime for 12 weeks Eszopiclone: 3mg capsule, once daily at bedtime
Measure Participants	14	13
Baseline	1.23 (0.30)	1.19 (0.15)
6 week follow-up	1.26 (0.31)	1.23 (0.25)
12 week follow-up	1.16 (0.24)	1.14 (0.19)

14. Primary Outcome

Title	Temporal Summation (TS)
Description	TS :maximum windup pain rating - first windup pain rating (0-100). Contact heat stimuli at non tissue damaging temperatures were delivered using computer driven, peltier-element-based stimulator (Medoc, TSA II), with a 9 cm2 probe applied to left forearm. In order to assess temporal summation, three sequences of 10 heat pulses each (with stimulus temperatures of 46 degrees C, 48 degrees C, and 50 degrees C, in random order) were applied to left dorsal forearm. The thermode remains in fixed position during administration of 10 heat pulses that constitute a sequence. Within each sequence, successive thermal pulses at a given temperature are delivered for a duration of approximately 0.5 sec each, with a 2.5-sec inter-pulse interval. The rate of rise & fall of the thermode temp. is set at the device max .of 10 degrees C / S. Subjects verbally rate the perceived intensity of each thermal pulse on a 0-100 rating scale & may terminate the procedure at any time.100=max tolerable intensity
Time Frame	Mean of baseline, 6 week follow-up and 12 week follow-up at 46, 48, and 50 degrees C

Outcome Measure Data

Analysis Population Description

Data was not included for all participants, as some were unable to complete the task or experienced technical difficulties.

Arm/Group Title	Placebo	Eszopiclone
Arm/Group Description	3mg placebo capsule, once daily at bedtime for 12 weeks Placebo: 3mg placebo capsule, once daily at bedtime	Eszopiclone 3mg capsules, once daily at bedtime for 12 weeks Eszopiclone: 3mg capsule, once daily at bedtime
Measure Participants	15	11
Baseline 46 degrees C	9.20 (16.08)	7.80 (12.93)
6 week follow-up 46 degrees C	6.41 (9.69)	6.50 (7.47)
12 week follow-up 46 degrees C	5.22 (7.45)	3.33 (7.07)
Baseline 48 degrees C	20.40 (41.90)	4.72 (6.77)
6 week follow-up 48 degrees C	5.75 (8.72)	8.11 (11.38)
12 week follow-up 48 degrees C	5.23 (8.70)	4.55 (4.13)
Baseline 50 degrees C	17.06 (23.09)	21.00 (20.25)
6 week follow-up 50 degrees C	13.27 (19.66)	18.00 (20.30)
12 week follow-up 50 degrees C	18.84 (23.82)	20.77 (28.92)

15. Primary Outcome

Title	Mean Level of Pain Experienced Throughout the Day
Description	Assessed using a Daily Pain Diary with a scale 0-100, 0 being no pain, 100 being the most severe/intense
Time Frame	Mean of baseline, 6 week follow-up and 12 week follow-up

Outcome Measure Data

Analysis Population Description

Data was not included for all participants, as some were unable to complete the task or experienced technical difficulties.

Arm/Group Title	Placebo	Eszopiclone
Arm/Group Description	3mg placebo capsule, once daily at bedtime for 12 weeks Placebo: 3mg placebo capsule, once daily at bedtime	Eszopiclone 3mg capsules, once daily at bedtime for 12 weeks Eszopiclone: 3mg capsule, once daily at bedtime
Measure Participants	15	10
Baseline	48.79 (19.63)	52.40 (18.87)
6 week follow-up	42.21 (18.34)	44.43 (28.39)
12 week follow-up	38.12 (19.11)	42.88 (25.53)

16. Primary Outcome

Title	Pain as Assessed by the Western Ontario and McMaster Universities Index of Osteoarthritis (WOMAC) Pain Severity Subscale
Description	The WOMAC is a quality of scale life made up of three domains, pain, stiffness, and disability which each comprising of 5, 2, and 7 questions, respectively. A VAS was used for each subscale. Pain was assessed on a scale of 0-100, with 0 being absolutely no pain and 100 being maximum pain.
Time Frame	Mean of baseline, 6 week follow-up and 12 week follow-up

Outcome Measure Data

Analysis Population Description

Data was not included for all participants, as some were unable to complete the task or experienced technical difficulties.

Arm/Group Title	Placebo	Eszopiclone
Arm/Group Description	3mg placebo capsule, once daily at bedtime for 12 weeks Placebo: 3mg placebo capsule, once daily at bedtime	Eszopiclone 3mg capsules, once daily at bedtime for 12 weeks Eszopiclone: 3mg capsule, once daily at bedtime
Measure Participants	14	14
Baseline	21.62 (10.75)	24.88 (13.79)
6 week follow-up	19.18 (12.03)	24.41 (13.74)
12 week follow-up	14.85 (11.04)	19.89 (14.15)

17. Secondary Outcome

Title	Heat Pain Threshold
Description	Contact heat stimuli at non tissue damaging temperatures were delivered using computer driven, peltier-element-based stimulator (Medoc, TSA II), with a 9 cm2 probe applied to the left forearm. The thermode was affixed snugly via Velcro straps to ensure even skin contact and repositioned to an adjacent site after each trial to minimize sensitizationHPTh was assessed on the left ventral forearm using an ascending method of limits paradigm; from a non-painful 32°C baseline, the temperature was steadily increased at 0.5°C/sec. Two trials of heat pain threshold were conducted. Averages of both trials are presented from respective time point below. Subjects push a button when the stimulus "first feels painful" The temperature (degrees Celsius) at the time button is pushed is automatically recorded.
Time Frame	Mean of baseline, 6 week follow-up and 12 week follow-up

Outcome Measure Data

Analysis Population Description

Data was not included for all participants, as some were unable to complete the task or experienced technical difficulties.

Arm/Group Title	Placebo	Eszopiclone
Arm/Group Description	3mg placebo capsule, once daily at bedtime for 12 weeks Placebo: 3mg placebo capsule, once daily at bedtime	Eszopiclone 3mg capsules, once daily at bedtime for 12 weeks Eszopiclone: 3mg capsule, once daily at bedtime
Measure Participants	15	14
Baseline	43.38 (4.71)	42.77 (3.51)
6 week follow-up	43.41 (5.41)	42.19 (3.95)
12 week follow-up	43.31 (4.61)	42.49 (4.38)

18. Secondary Outcome

Title	Heat Pain Tolerance (HPTOL)
Description	Contact heat stimuli at non tissue damaging temperatures were delivered using computer driven, peltier-element-based stimulator (Medoc, TSA II), with a 9 cm2 probe applied to the left forearm. The thermode was affixed snugly via Velcro straps to ensure even skin contact and repositioned to an adjacent site after each trial to minimize sensitization. HPTOL was assessed on the left ventral forearm using an ascending method of limits paradigm; from a non-painful 32°C baseline, the temperature was steadily increased at 0.5°C/sec. Two trials of HPTOL were conducted. An average of both trials at each respective time point is presented below. Subjects push a button when the stimulus "becomes intolerable." The temperature (degrees Celsius) at the time button is pushed to terminate the stimulation is automatically recorded.
Time Frame	Mean of baseline, 6 week follow-up and 12 week follow-up

Outcome Measure Data

Analysis Population Description

Data was not included for all participants, as some were unable to complete the task or experienced technical difficulties.

Arm/Group Title	Placebo	Eszopiclone
Arm/Group Description	3mg placebo capsule, once daily at bedtime for 12 weeks Placebo: 3mg placebo capsule, once daily at bedtime	Eszopiclone 3mg capsules, once daily at bedtime for 12 weeks Eszopiclone: 3mg capsule, once daily at bedtime
Measure Participants	15	14
Baseline	47.65 (2.28)	46.56 (2.80)
6 week follow-up	47.54 (2.26)	46.87 (3.56)
12 week follow-up	47.92 (2.24)	46.67 (3.93)

19. Secondary Outcome

Title	Pressure Pain Threshold
Description	A Somedic algometer was used to assess pressure pain threshold (PPTh) similar to previous studies. The algometer's 1cm2 rubber probe was placed over the muscle belly, with the pressure increased steadily at a constant rate (30kPA/Sec), until the subject indicated that s/he "first felt pain." PPTh was assessed 2 times each, bilaterally, at (in a randomized order) the masseter muscle trapezius muscle, and at the proximal third of the brachioradialis muscle (forearm). The scores from each location were averaged for each participant at that respective time point. The same site was never stimulated consecutively. At least 90 s were maintained between successive stimuli
Time Frame	Mean of baseline, 6 week follow-up and 12 week follow-up

Outcome Measure Data

Analysis Population Description

Data was not included for all participants, as some were unable to complete the task or experienced technical difficulties.

Arm/Group Title	Placebo	Eszopiclone
Arm/Group Description	3mg placebo capsule, once daily at bedtime for 12 weeks Placebo: 3mg placebo capsule, once daily at bedtime	Eszopiclone 3mg capsules, once daily at bedtime for 12 weeks Eszopiclone: 3mg capsule, once daily at bedtime
Measure Participants	15	14
Baseline	300.91 (111.13)	267.93 (111.50)
6 week follow-up	322.24 (107.82)	287.29 (107.01)
12 week follow-up	381.92 (199.33)	309.15 (81.16)

20. Secondary Outcome

Title	Quality of Life as Assessed by the Western Ontario and McMaster Universities Index of Osteoarthritis (WOMAC) Disability Subscale
Description	The WOMAC is a quality of scale life made up of three domains, pain, stiffness, and disability which each comprising of 5, 2, and 7 questions, respectively. A VAS was used for each subscale. Disability was assessed on a VAS of 0-100, with 0 being absolutely no disability and 100 being maximum disability.
Time Frame	Mean of baseline, 6 week follow-up and 12 week follow-up

Outcome Measure Data

Analysis Population Description

Data was not included for all participants, as some were unable to complete the task or experienced technical difficulties.

Arm/Group Title	Placebo	Eszopiclone
Arm/Group Description	3mg placebo capsule, once daily at bedtime for 12 weeks Placebo: 3mg placebo capsule, once daily at bedtime	Eszopiclone 3mg capsules, once daily at bedtime for 12 weeks Eszopiclone: 3mg capsule, once daily at bedtime
Measure Participants	14	14
Baseline	64.32 (41.26)	74.69 (46.18)
6 week follow-up	62.26 (45.878)	79.71 (47.79)
12 week follow-up	56.13 (48.11)	70.44 (50.75)

21. Secondary Outcome

Title	Quality of Life as Assessed by the Short Form-36 (SF-36) Physical Health Component Summary
Description	The SF-36 is a broad, well normed measure of quality of life, comprised of 36 questions aggregated into 8 domains/dimensions. The Physical Component Summary was used here as a global index of physical health functioning. Scale 0-100, with 0 being worst functional level, 100 being the best.
Time Frame	Mean of baseline, 6 week follow-up and 12 week follow-up

Outcome Measure Data

Analysis Population Description

Data was not included for all participants, as some were unable to complete the task or experienced technical difficulties.

Arm/Group Title	Placebo	Eszopiclone
Arm/Group Description	3mg placebo capsule, once daily at bedtime for 12 weeks Placebo: 3mg placebo capsule, once daily at bedtime	Eszopiclone 3mg capsules, once daily at bedtime for 12 weeks Eszopiclone: 3mg capsule, once daily at bedtime
Measure Participants	14	14
Baseline	57.61 (25.91)	52.73 (23.38)
6 week follow-up	60.60 (27.48)	49.44 (28.94)
12 week follow-up	65.00 (21.69)	49.40 (28.41)

22. Secondary Outcome

Title	Quality of Life as Assessed by the Short Form-36 (SF-36) Mental Health Component Summary
Description	The SF-36 is a broad, well normed measure of quality of life, comprised of 36 questions aggregated into 8 domains/dimensions. The Mental Component Summary was used here as a global index of mental health functioning. Scale 0-100, with 0 being worst functional level, 100 being the best.
Time Frame	Mean of baseline, 6 week follow-up and 12 week follow-up

Outcome Measure Data

Analysis Population Description

Data was not included for all participants, as some were unable to complete the task or experienced technical difficulties.

Arm/Group Title	Placebo	Eszopiclone
Arm/Group Description	3mg placebo capsule, once daily at bedtime for 12 weeks Placebo: 3mg placebo capsule, once daily at bedtime	Eszopiclone 3mg capsules, once daily at bedtime for 12 weeks Eszopiclone: 3mg capsule, once daily at bedtime
Measure Participants	14	14
Baseline	50.40 (9.56)	45.78 (7.88)
6 week follow-up	51.68 (7.73)	45.86 (7.06)
12 week follow-up	50.71 (5.89)	47.04 (11.05)

23. Secondary Outcome

Title	Joint Stiffness as Assessed by the Western Ontario and McMaster Universities Index of Osteoarthritis (WOMAC) Joint Stiffness Subscale
Description	The WOMAC is a quality of scale life made up of three domains, pain, stiffness, and disability which each comprising of 5, 2, and 7 questions, respectively. A VAS was used for each subscale. Joint Stiffness was assessed on a VAS scale of 0-20, with 0 being no joint stiffness, and 20 being maximum stiffness.
Time Frame	Mean of baseline, 6 week follow-up and 12 week follow-up

Outcome Measure Data

Analysis Population Description

Data was not included for all participants, as some were unable to complete the task or experienced technical difficulties.

Arm/Group Title	Placebo	Eszopiclone
Arm/Group Description	3mg placebo capsule, once daily at bedtime for 12 weeks Placebo: 3mg placebo capsule, once daily at bedtime	Eszopiclone 3mg capsules, once daily at bedtime for 12 weeks Eszopiclone: 3mg capsule, once daily at bedtime
Measure Participants	14	14
Baseline	10.17 (5.60)	12.86 (5.05)
6 week follow-up	7.55 (5.74)	12.17 (4.41)
12 week follow-up	6.86 (5.89)	11.32 (5.61)

Adverse Events

Time Frame	Participants were followed for study duration, up to 12 weeks
Arm/Group Title	Placebo		Eszopiclone
Arm/Group Description	3mg placebo capsule, once daily at bedtime for 12 weeks Placebo: 3mg placebo capsule, once daily at bedtime		Eszopiclone 3mg capsules, once daily at bedtime for 12 weeks Eszopiclone: 3mg capsule, once daily at bedtime
All Cause Mortality
	Placebo		Eszopiclone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/14 (0%)
Serious Adverse Events
	Placebo		Eszopiclone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/14 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Eszopiclone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/16 (31.3%)		7/14 (50%)
Product Issues
Other Mild to Moderate (Not Recorded)	5/16 (31.3%)	5	6/14 (42.9%)	6
Psychiatric disorders
Restlessness, anxiety, agitation	0/16 (0%)	0	1/14 (7.1%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.