REST-IT: Reducing Suicidal Ideation Through Insomnia Treatment

• Sponsor: Augusta University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01689909
• Collaborator: National Institute of Mental Health (NIMH) (NIH), Wake Forest University Health Sciences (Other), University of Wisconsin, Madison (Other), Duke University (Other)
• Enrollment: 103
• Locations: 4
• Arms: 2
• Actual Duration (Months): 60.8
• Patients Per Site: 25.8
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

Epidemiologic reports have linked insomnia to suicidal ideation and suicide death. However, no studies have determined whether treating insomnia decreases the risk of suicidality. We have new data indicating that (1) the link between insomnia and suicidal ideation holds true in clinical trials of depressed insomniacs, (2) dysfunctional cognitions about sleep are related to suicidal ideas, and (3) treatment of insomnia with hypnotics leads to a reduction of suicidal ideation. We now propose to test whether cautious use of hypnotics in suicidal, depressed insomniacs may reduce suicide risk in a multi-site clinical trial.

Condition or Disease	Intervention/Treatment	Phase
Insomnia; Depression; Suicidal Ideation	Drug: Zolpidem-CR; Drug: Placebo	Phase 4

Detailed Description

Primary Aim: We will assess the effect of treating insomnia with hypnotic medication on the intensity of suicidal ideation in depressed outpatients with insomnia and suicidal ideation.

-Hypothesis 1. Treatment of depressed, insomniac and suicidal outpatients with open-label fluoxetine (FLX) and blinded zolpidem controlled release (ZOL) will reduce suicidal ideation more than treatment with FLX and blinded placebo.

Secondary Aim: We will examine whether reduced suicidal ideation in depressed insomniacs is mediated through reduced dysfunctional beliefs about sleep, reduced hopelessness, or fewer nightmares.

• Hypothesis 2a. Reduction in suicidal ideation will be mediated through reductions in dysfunctional beliefs about sleep.

• Hypothesis 2b. Reduction in suicidal ideation will be mediated through reductions in hopelessness.

• Hypothesis 2c. Reduction in suicidal ideation is mediated through fewer nightmares.

Tertiary Aim: We will confirm findings from our prior pilot studies that treatment of insomnia in depressed insomniacs leads to improvements in health-related quality of life, especially in women.

Exploratory Aim: We will archive actigraphy data to permit future examination to confirm our preliminary data that actigraphic activity decreases as suicidal ideation resolves.

Overview of the Need for and Management of a Collaborative Application: The sample sizes required to satisfy the Aims are relatively large, necessitating the pooled recruiting resources of 3 sites. Georgia Regents University (GRU) will serve both as the coordinating/data management site, as well as a recruiting site, with Duke and Wisconsin as recruiting sites. Project management will be coordinated through an Executive Committee of site principal investigators, under the supervision of a Data and Safety Monitoring Board.

Impact on the Field: This application has the potential to change providers' practice in the approach to treating insomnia in depressed patients with mild-moderate suicidal ideation. It may also reveal the mechanisms whereby insomnia increases the risk for suicidal ideation and behavior, and begin to examine whether there is an actigraphic "signature" for reductions in suicidal ideation. When these lessons are applied to the clinical world, they can be applied with low cost.

Study Design

• Study Type: Interventional
• Actual Enrollment: 103 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Reducing Suicidal Ideation Through Insomnia Treatment
• Actual Study Start Date: Dec 6, 2012
• Actual Primary Completion Date: Jun 1, 2017
• Actual Study Completion Date: Jan 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Zolpidem-CR Zolpidem 6.25 or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks	Drug: Zolpidem-CR; Zolpidem 6.25 mg or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks; Other Names: Ambien CR
Placebo Comparator: Placebo Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks	Drug: Placebo; Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks

Outcome Measures

Primary Outcome Measures

1. Scale for Suicide Ideation Index (SSI) [Over 8 weeks of treatment]

   This is the total score for the Scale for Suicide Ideation. It has 19 items, each scored 0-2, for a maximum of 38 points. Higher scores indicate worse suicidal ideation

2. Columbia Suicide Severity Rating Scale (C-SSRS): the Suicidal Ideation Scale [8 weeks of treatment]

   The suicide ideation scale of the C-SSRS is rated 0-5, with "0" meaning no suicidal ideation, "1" meaning a wish t be dead, "2" meaning non-specific active suicidal thoughts, "3" meaning active suicidal ideation with any methods but no plan or intent, "4" meaning active suicidal ideation with some intent but no specific plan, and "5" meaning active suicidal ideation with intent and a specific plan

Secondary Outcome Measures

1. Dysfunctional Beliefs and Attitudes About Sleep [8 weeks of treatment]

   The Dysfunctional Beliefs and Attitudes About Sleep scale has 16 items and is self administered. Each item is scored 0-10. The total score is an average of the scores of the 16 items. Hence the range of the total score is also 0-10, with higher scores indicating greater dysfunctional beliefs about sleep

2. Disturbing Dreams and Nightmares Severity Index (DDNSI) [8 weeks of treatment]

   This self-rated scale has 5 items, with asymmetric weighting of each item. The range of the total score is 0-37, with higher scores indicating worse nightmares

3. Beck Hopelessness Scale (BHS) [8 weeks of treatment]

   The Beck Hopelessness Scale is self administered and has 20 'true/false' choices. Some items are reversed scored. The range of scores for the total is 0-20, with higher scores indicating greater hopelessness

4. Hamilton Rating Scale for Depression (HAM-D) [8 weeks of treatment]

   This version of the Hamilton Rating Scale for Depression uses 24 items, with a possible total score ranging from 0-74, with higher scores indicating worse depression

5. Insomnia Severity Index (ISI) [8 weeks of treatment]

   The Insomnia Severity Index is self rated. It has 7 items, each scored 0-4. Therefore the range of scores is 0-28, with higher scores indicating worse insomnia

Other Outcome Measures

1. Basis-32 - the Daily Living and Role Functioning (DLRF) Subscale [8 weeks of treatment]

   This is one of the subscales of the Basis 32. It is self-administered. This subscale has 7 items, each scored 0-4. The totals score is an average of the scores of these 7 items. Higher scores indicate more difficulty with daily living and role functioning.

2. Actigraphy [8 weeks of treatment]

   This device measures arm motion over time, reported as "average actigraphic activity Level". The scale is reported as a continuous measure ranging from 0-200, and reported as the average score for each hour for all 24-hours of the day. Higher score represent greater c=activity at that point in time

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Persons 18-65 years of age

• Persons with confirmed DSM-IV diagnosis of MDE by SCID

• Persons with Research Diagnostic Criteria diagnosis of insomnia

• Persons free of all psychotropic medications for one week before baseline assessment, except that prior FLX treatment will require 4 weeks of abstinence, and MAOIs will require 2 weeks of abstinence.

• Persons with Scale for Suicide Ideation (SSI) scores >2

• Persons with Hamilton Rating Scale for Depression (HRSD24) score >20

• Persons with Mini Mental State Exam (MMSE) score >24

• Persons with Insomnia Severity Index (ISI) score > 7

• Persons with habitual sleep latency > or = 30 minutes or wake time in the middle of the night of > or = 30 minutes, and sleep efficiency < 85%

Exclusion Criteria:

• Non-English speaking, reading, writing persons

• Persons who pose imminent danger to self or others

• Persons with severe suicidal ideation (C-SSRS Suicidal Ideation Score >3)

• Persons with clinical diagnosis of dementia

• Persons with active or past diagnosis of alcohol or substance abuse, bipolar disorder, schizophrenia per the SCID

• Persons who screen positive for moderate-severe sleep apnea (AHI >10) or a prior sleep laboratory-confirmed diagnosis of a primary sleep disorder, such as sleep apnea or periodic limb movement disorder.

• Persons with BMI > 50

• Persons with a self-reported history of napping > 2 times per week (as these are associated with sleep apnea and periodic limb movement disorder in depressed insomniacs)

• Persons who might be harmed by exposure to hypnotics, including pregnant women and patients with respiratory conditions

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Georgia Regents University	Augusta	Georgia	United States	30912
2	Duke University School of Medicine	Durham	North Carolina	United States	27710
3	Wake Forest University School of Medicine	Wake Forest	North Carolina	United States	27157
4	University of Wisconsin- Madison	Madison	Wisconsin	United States	53719

Sponsors and Collaborators

• Augusta University
• National Institute of Mental Health (NIMH)
• Wake Forest University Health Sciences
• University of Wisconsin, Madison
• Duke University

Investigators

• Principal Investigator: William V McCall, MD, MS, Augusta University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 8, 2014

More Information

Publications

None provided.

• Responsible Party: Augusta University
• ClinicalTrials.gov Identifier: NCT01689909
• Other Study ID Numbers: 1R01MH095776-01A1; 1R01MH095776
• First Posted: Sep 21, 2012
• Last Update Posted: Feb 16, 2022
• Last Verified: Feb 1, 2022

• Keywords provided by Augusta University: Insomnia; Depression; Suicidal ideation; Zolpidem CR; Placebo
• Additional relevant MeSH terms: Sleep Initiation and Maintenance Disorders; Depression; Suicidal Ideation; Zolpidem

Study Results

Participant Flow

Arm/Group Title	Zolpidem-CR	Placebo
Arm/Group Description	Zolpidem 6.25 or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks Zolpidem-CR: Zolpidem 6.25 mg or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks	Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks Placebo: Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks
Period Title: Overall Study
STARTED	51	52
COMPLETED	51	52
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Zolpidem-CR	Placebo	Total
Arm/Group Description	Zolpidem 6.25 or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks Zolpidem-CR: Zolpidem 6.25 mg or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks	Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks Placebo: Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks	Total of all reporting groups
Overall Participants	51	52	103
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	51 100%	52 100%	103 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	39.7 (14.5)	41.2 (12.0)	40.5 (13.2)
Sex: Female, Male (Count of Participants)
Female	32 62.7%	32 61.5%	64 62.1%
Male	19 37.3%	20 38.5%	39 37.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	4 7.8%	1 1.9%	5 4.9%
Not Hispanic or Latino	47 92.2%	51 98.1%	98 95.1%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	5 9.8%	2 3.8%	7 6.8%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	12 23.5%	16 30.8%	28 27.2%
White	34 66.7%	34 65.4%	68 66%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	51 100%	52 100%	103 100%
Scale for Suicide Ideation (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	12.2 (5.3)	11.8 (5.3)	12.0 (5.3)
Columbia Suicide Severity Rating Scale (C-SSRS) - suicide ideation scale (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	1.71 (10.3)	1.58 (10.2)	1.64 (1.02)
Hamilton Rating Scale for Depression -24 (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	28.7 (4.7)	29.6 (7.0)	29.1 (5.9)
Disturbing Dreams Nightmare Severity Index (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	10.5 (8.8)	10.2 (7.7)	10.3 (8.2)
Insomnia Severity Index (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	20.6 (3.9)	21.1 (4.3)	20.8 (4.1)

Outcome Measures

1. Primary Outcome

Title	Scale for Suicide Ideation Index (SSI)
Description	This is the total score for the Scale for Suicide Ideation. It has 19 items, each scored 0-2, for a maximum of 38 points. Higher scores indicate worse suicidal ideation
Time Frame	Over 8 weeks of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Zolpidem-CR	Placebo
Arm/Group Description	Zolpidem 6.25 or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks Zolpidem-CR: Zolpidem 6.25 mg or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks	Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks Placebo: Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks
Measure Participants	51	52
Least Squares Mean (Standard Error) [units on a scale]	4.66 (0.58)	5.25 (0.59)

2. Primary Outcome

Title	Columbia Suicide Severity Rating Scale (C-SSRS): the Suicidal Ideation Scale
Description	The suicide ideation scale of the C-SSRS is rated 0-5, with "0" meaning no suicidal ideation, "1" meaning a wish t be dead, "2" meaning non-specific active suicidal thoughts, "3" meaning active suicidal ideation with any methods but no plan or intent, "4" meaning active suicidal ideation with some intent but no specific plan, and "5" meaning active suicidal ideation with intent and a specific plan
Time Frame	8 weeks of treatment

Outcome Measure Data

Analysis Population Description

all evaluable randomized participants

Arm/Group Title	Zolpidem-CR	Placebo
Arm/Group Description	Zolpidem 6.25 or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks Zolpidem-CR: Zolpidem 6.25 mg or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks	Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks Placebo: Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks
Measure Participants	51	52
Least Squares Mean (Standard Error) [units on a scale]	0.5447 (0.0869)	0.8067 (0.0875)

3. Secondary Outcome

Title	Dysfunctional Beliefs and Attitudes About Sleep
Description	The Dysfunctional Beliefs and Attitudes About Sleep scale has 16 items and is self administered. Each item is scored 0-10. The total score is an average of the scores of the 16 items. Hence the range of the total score is also 0-10, with higher scores indicating greater dysfunctional beliefs about sleep
Time Frame	8 weeks of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Zolpidem-CR	Placebo
Arm/Group Description	Zolpidem 6.25 or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks Zolpidem-CR: Zolpidem 6.25 mg or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks	Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks Placebo: Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks
Measure Participants	51	52
Least Squares Mean (Standard Error) [units on a scale]	6.03 (0.171)	6.07 (0.171)

4. Secondary Outcome

Title	Disturbing Dreams and Nightmares Severity Index (DDNSI)
Description	This self-rated scale has 5 items, with asymmetric weighting of each item. The range of the total score is 0-37, with higher scores indicating worse nightmares
Time Frame	8 weeks of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Zolpidem-CR	Placebo
Arm/Group Description	Zolpidem 6.25 or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks Zolpidem-CR: Zolpidem 6.25 mg or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks	Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks Placebo: Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks
Measure Participants	51	52
Least Squares Mean (Standard Error) [units on a scale]	5.74 (0.710)	6.44 (0.718)

5. Secondary Outcome

Title	Beck Hopelessness Scale (BHS)
Description	The Beck Hopelessness Scale is self administered and has 20 'true/false' choices. Some items are reversed scored. The range of scores for the total is 0-20, with higher scores indicating greater hopelessness
Time Frame	8 weeks of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Zolpidem-CR	Placebo
Arm/Group Description	Zolpidem 6.25 or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks Zolpidem-CR: Zolpidem 6.25 mg or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks	Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks Placebo: Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks
Measure Participants	51	52
Least Squares Mean (Standard Error) [units on a scale]	9.40 (0.58)	9.63 (0.58)

6. Secondary Outcome

Title	Hamilton Rating Scale for Depression (HAM-D)
Description	This version of the Hamilton Rating Scale for Depression uses 24 items, with a possible total score ranging from 0-74, with higher scores indicating worse depression
Time Frame	8 weeks of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Zolpidem-CR	Placebo
Arm/Group Description	Zolpidem 6.25 or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks Zolpidem-CR: Zolpidem 6.25 mg or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks	Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks Placebo: Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks
Measure Participants	51	52
Least Squares Mean (Standard Error) [units on a scale]	14.93 (0.87)	15.89 (0.88)

7. Secondary Outcome

Title	Insomnia Severity Index (ISI)
Description	The Insomnia Severity Index is self rated. It has 7 items, each scored 0-4. Therefore the range of scores is 0-28, with higher scores indicating worse insomnia
Time Frame	8 weeks of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Zolpidem-CR	Placebo
Arm/Group Description	Zolpidem 6.25 or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks Zolpidem-CR: Zolpidem 6.25 mg or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks	Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks Placebo: Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks
Measure Participants	51	52
Least Squares Mean (Standard Error) [units on a scale]	11.28 (0.62)	13.72 (0.63)

8. Other Pre-specified Outcome

Title	Basis-32 - the Daily Living and Role Functioning (DLRF) Subscale
Description	This is one of the subscales of the Basis 32. It is self-administered. This subscale has 7 items, each scored 0-4. The totals score is an average of the scores of these 7 items. Higher scores indicate more difficulty with daily living and role functioning.
Time Frame	8 weeks of treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Zolpidem-CR	Placebo
Arm/Group Description	Zolpidem 6.25 or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks Zolpidem-CR: Zolpidem 6.25 mg or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks	Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks Placebo: Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks
Measure Participants	51	52
Least Squares Mean (Standard Error) [units on a scale]	1.51 (0.102)	1.60 (0.102)

9. Other Pre-specified Outcome

Title	Actigraphy
Description	This device measures arm motion over time, reported as "average actigraphic activity Level". The scale is reported as a continuous measure ranging from 0-200, and reported as the average score for each hour for all 24-hours of the day. Higher score represent greater c=activity at that point in time
Time Frame	8 weeks of treatment

Outcome Measure Data

Analysis Population Description

participants with depression, insomnia, and suicidality

Arm/Group Title	Scale for Suicide Ideation Score Greater Than or Equal to 6	Scale for Suicide Ideation Score Less Than 6
Arm/Group Description	Participants with a baseline Scale for Suicide Ideation Score Greater than or Equal to 6	Participants with Scale for Suicide Ideation Score less than 6
Measure Participants	37	23
Mean (Standard Error) [units on a scale]	150 (30)	170 (30)

Adverse Events

Time Frame	8 weeks randomized care and 2 weeks of follow up after the end of randomized care
Arm/Group Title	Zolpidem-CR		Placebo
Arm/Group Description	Zolpidem 6.25 or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks Zolpidem-CR: Zolpidem 6.25 mg or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks		Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks Placebo: Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks
All Cause Mortality
	Zolpidem-CR		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/51 (0%)		0/52 (0%)
Serious Adverse Events
	Zolpidem-CR		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/51 (2%)		0/52 (0%)
Pregnancy, puerperium and perinatal conditions
pregnancy then miscarriage	1/51 (2%)		0/52 (0%)
Other (Not Including Serious) Adverse Events
	Zolpidem-CR		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	31/51 (60.8%)		37/52 (71.2%)
Gastrointestinal disorders
nausea and diarrhea	9/51 (17.6%)	14	9/52 (17.3%)	14
General disorders
Other	4/51 (7.8%)	14	13/52 (25%)	28
Nervous system disorders
headache	6/51 (11.8%)	9	6/52 (11.5%)	11
Respiratory, thoracic and mediastinal disorders
cold symptoms and flu	12/51 (23.5%)	21	9/52 (17.3%)	9

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.