Sleep Loss and Mechanisms of Impaired Glucose Metabolism

• Sponsor: Brigham and Women's Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT00555750
• Collaborator: Sunovion (Industry), Mclean Hospital (Other), National Center for Research Resources (NCRR) (NIH)
• Enrollment: 20
• Location: 1
• Arms: 2
• Duration (Months): 29
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

The purpose of this study is to test the effects of sleep and eszopiclone, a drug that helps people sleep, on how the body processes glucose (sugar). Eszopiclone is approved by the U.S. Food and Drug Administration (FDA) for sale for the treatment of insomnia. It is marketed in the United States as LUNESTA.

Main Hypothesis: Primary insomnia is associated with impairments of glucose metabolism that can be reversed by two months of eszopiclone for the primary insomnia

Condition or Disease	Intervention/Treatment	Phase
Primary Insomnia	Drug: eszopiclone; Drug: placebo	N/A

Detailed Description

Insomnia is the most common sleep disorder, affecting nearly one-third of all adults in any given year, and chronically affecting 10-15% of the adult population. Reduced sleep time, independent of insomnia, has been associated with a variety of deleterious long term effects, including an increased risk of incident myocardial infarction and symptomatic diabetes. Chronic partial sleep loss or insomnia may impair glucose metabolism in the short term and are associated with the development of diabetes in the long term. Although the extent of sleep loss is more acute in the laboratory-based 'sleep debt' studies of healthy volunteers, chronic primary insomnia patients exhibit 'hyperarousal' (hypercortisolemia in the afternoon and evening, accelerated metabolism) similar to that seen with acute sleep deprivation. In addition, degradations of sleep quantity and quality in primary insomnia have been attributed to cognitive and somatic hyperarousal in the sleep setting. study examines and quantifies in adult men and women the link between primary insomnia and impaired glucose tolerance. This study examines the extent which adequate treatment of primary insomnia reverses impairments of glucose metabolism. If abnormalities of glucose metabolism are reversible, this study will demonstrate the importance of treatment of chronic primary insomnia.

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Basic Science
• Official Title: The Effects of Eszopiclone Treatment (3mg for Two Months) to Counteract the Adverse Metabolic Consequences of Primary Insomnia
• Study Start Date: Mar 1, 2006
• Actual Primary Completion Date: Jul 1, 2008
• Actual Study Completion Date: Aug 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: eszopiclone (3mg) active medication (eszopiclone 3mg tablet) by mouth nightly 30 min before bed	Drug: eszopiclone; 3mg tablet, by mouth nightly 30 min before bed, for two months; Other Names: Lunesta
Placebo Comparator: placebo identical placebo tablet by mouth nightly 30 min before bed	Drug: placebo; inactive placebo tablet, by mouth nightly 30 minutes before bed, for two months

Outcome Measures

Primary Outcome Measures

1. Change in Glucose Tolerance (Kg) in Response to Insulin-modified Intravenous Glucose Tolerance Test [baseline and 2 months post-treatment]

   Difference in glucose tolerance (Kg) in response to insulin-modified intravenous glucose tolerance test. Glucose tolerance was calculated as the slope of the natural log of declining glucose values from minute 5 to minute 19 post-infusion. By convention, this negative slope is multiplied by -1, in other words, expressed as a rate of disposal.

Secondary Outcome Measures

1. Acute Insulin Response to Glucose (AIRg) [baseline and 2 months post-treatment]

   Change over two months in 1st phase Insulin secretion

2. Change in Insulin Sensitivity (SI) [baseline and 2 months post-treatment]

   Insulin sensitivity index (SI) "was defined in quantitative terms as the effect of insulin to catalyse the disappearance of glucose from plasma." [R. Bergman, Horm Res 2005;64(suppl 3):8-15]. SI calculated using Bergman's Minimal model analyses (Minmod Millennium 2000; R. Bergman, University of South- ern California, Los Angeles, CA)

3. Change in Glucose Effectiveness (SG) [baseline and 2 months post-treatment]

   Glucose effectiveness was defined as "the ability of glucose itself to enhance its own disappearance independent of an increment in insulin." [R. Bergman, Horm Res 2005;64(suppl 3):8-15]. SG calculated using Bergman's Minimal model analyses (Minmod Millennium 2000; R. Bergman, University of South- ern California, Los Angeles, CA)

4. Change in HbA1c Levels [baseline and 2 months post-treatment]

   Difference in HbA1c levels following two months treatment with eszopiclone versus placebo

5. Pre-Treatment Leptin Levels [baseline]

   Leptin Levels prior to two months treatment with eszopiclone or placebo, measure after an overnight fast

6. Post-treatment Leptin Levels [two months post-treatment]

   Leptin levels following two months treatment with 3mg eszopiclone or placebo, measured after an overnight fast

7. Pre-treatment Ghrelin Levels [baseline]

   Ghrelin levels prior to two months treatment with 3mg eszopiclone or placebo, measured after an overnight fast

8. Post-treatment Ghrelin Levels [2 months post-treatment]

   Ghrelin levels following two months treatment with 3mg eszopiclone or placebo, measured after an overnight fast

9. Change in Subjective Sleepiness as Measured on the Karolinska Sleepiness Scale (KSS) [baseline and 2 months post-treatment]

   At visits before and after two months treatment with 3mg eszopiclone or placebo, subjects completed a short test battery including the Karolinska Sleepiness Scale (KSS) every three hours during wake periods. KSS is a single-item scale of sleepiness on a scale from 1 ("very alert") to 9 ("very sleepy, fighting sleep, an effort to keep awake"). Subjective sleepiness was defined as mean deviation from baseline KSS.

10. Change in Mean Lapses of Attention [baseline and 2 months post-treatment]

    At visits before and after two months treatment with 3mg eszopiclone or placebo, subjects completed a short test battery every three hours during wake periods. The battery included the Psychomotor Vigilance Task (PVT). The PVT involved a 10-minute visual reaction time (RT) performance test in which the subject was instructed to maintain the fastest possible RT to a simple visual stimulus. Lapses of attention refer to the number of times the subject failed to respond to the signal within 500ms. Mean lapses per test across 6 tests given a 4 hour intervals during normal waking hours (and not during the IVGTT) during the 30-hr were compared for the post-treatment visit as the absolute deviation from the baseline mean lapses/test.

11. Change in Total Sleep Time as Reported in Sleep Diaries [baseline and 2 months post-treatment]

    Total sleep time reported on sleep diaries prior to treatment with 3mg eszopiclone or placebo. Change defined as baseline minus post-treatment).

12. Change in Total Sleep Time Measured by PSG [baseline and 2 months post-treatment]

    Change (baseline minus post-treatment) in total sleep time measured by polysomnography after two months treatment with 3mg eszopiclone or placebo

Eligibility Criteria

Criteria

• Ages Eligible for Study: 25 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age 25-55

• Complaint of insomnia of at least 6 months duration

• DSM-IV diagnosis of Primary Insomnia

• Sleep diary: mean Total Sleep Time < 6 hours and a mean total wake time (sleep latency

• wake after sleep onset) of greater than 60 minutes (in previous 14 days as recorded on sleep diary)

• A willingness to comply with study procedures

• If of child-bearing potential, using a medically-accepted method of birth control, including abstinence, barrier method with spermicide, steroidal contraceptive (oral, transdermal, implanted, and injected) in conjunction with a barrier method, and intrauterine device [IUD])

Exclusion Criteria:

• Current diagnosis of DSM-IV Axis I disorder other than Primary Insomnia

• Regular treatment (more than 1 time/week) with CNS active medication within 1 month of fist inpatient visit

• Treatment with medications that interfere with glucose metabolism including anti-diabetic medications or steroidal contraceptives

• Uncontrolled medical illness that would interfere with participation in the study

• Body Mass Index >32 or <19.8

• Current symptoms or diagnosis of any moderate to severe sleep disorder other than insomnia

• No menopausal or peri-menopausal symptoms that disrupt sleep

• Pregnant, lactating or planning to become pregnant

• Consumption of > 2 caffeinated beverages per day (including coffee, tea and/or other caffeine-containing beverages or food) during 3 weeks prior to the start of the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Brigham and Women's Hospital, Division of Sleep Medicine	Boston	Massachusetts	United States	02115

Sponsors and Collaborators

• Brigham and Women's Hospital
• Sunovion
• Mclean Hospital
• National Center for Research Resources (NCRR)

Investigators

• Principal Investigator: John W Winkelman, MD, PhD, Brigham and Women's Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

• Ayas NT, White DP, Al-Delaimy WK, Manson JE, Stampfer MJ, Speizer FE, Patel S, Hu FB. A prospective study of self-reported sleep duration and incident diabetes in women. Diabetes Care. 2003 Feb;26(2):380-4.
• Ayas NT, White DP, Manson JE, Stampfer MJ, Speizer FE, Malhotra A, Hu FB. A prospective study of sleep duration and coronary heart disease in women. Arch Intern Med. 2003 Jan 27;163(2):205-9.
• Beck-Nielsen H, Henriksen JE, Alford F, Hother-Nielson O. In vivo glucose metabolism, insulin secretion and, insulin action in Europids with non-insulin-dependent diabetes mellitus (NIDDM) and their first-degree relatives. Diabet Med. 1996 Sep;13(9 Suppl 6):S78-84. Review.
• Belenky G, Wesensten NJ, Thorne DR, Thomas ML, Sing HC, Redmond DP, Russo MB, Balkin TJ. Patterns of performance degradation and restoration during sleep restriction and subsequent recovery: a sleep dose-response study. J Sleep Res. 2003 Mar;12(1):1-12.
• Boyne MS, Saudek CD. Effect of insulin therapy on macrovascular risk factors in type 2 diabetes. Diabetes Care. 1999 Apr;22 Suppl 3:C45-53. Review.
• Buxton OM, Spiegel K and Van Cauter E. Modulation of endocrine function and metabolism by sleep and sleep loss. In: Sleep Medicine, edited by Lee-Chiong M, Carskadon M and Sateia M. Philadelphia: Hanley & Belfus, Inc., 2002, p. 59-69.
• Buysse DJ, Jarrett DB, Miewald JM, Kupfer DJ, Greenhouse JB. Minute-by-minute analysis of REM sleep timing in major depression. Biol Psychiatry. 1990 Nov 15;28(10):911-25.
• Czeisler CA, Winkelman JW and Richardson GS. Disorders of sleep and circadian rhythms. In: Harrison's Principles of Internal Medicine, edited by Braunwald E, Fauci AS, Kasper DL, Hauser SL, Longo DL and Jameson JL. New York: McGraw-Hill,Inc., 2000, p. 1-78.
• Dijk DJ, Duffy JF, Czeisler CA. Circadian and sleep/wake dependent aspects of subjective alertness and cognitive performance. J Sleep Res. 1992 Jun;1(2):112-7.
• Dinges DF and Powell JW. Microcomputer analyses of performance on a portable, simple visual RT task during sustained operations. Behavior Research Methods, Instruments & Computers 17: 652-655, 1985.
• Dinges DF, Kribbs NB, Bates BL and Carlin MM. A very brief probed-recall memory task: Sensitivity to sleep loss. Sleep Res 22: 330, 1993.
• Gillberg M, Kecklund G, Akerstedt T. Relations between performance and subjective ratings of sleepiness during a night awake. Sleep. 1994 Apr;17(3):236-41.
• Gottlieb DJ, Punjabi NM, Newman AB, Resnick HE, Redline S, Baldwin CM, Nieto FJ. Association of sleep time with diabetes mellitus and impaired glucose tolerance. Arch Intern Med. 2005 Apr 25;165(8):863-7.
• Hoddes E, Dement WC and Zarcone V. The development and use of the Stanford Sleepiness Scale (SSS). Psychophysiol 9: 150, 1971.
• King H, Aubert RE, Herman WH. Global burden of diabetes, 1995-2025: prevalence, numerical estimates, and projections. Diabetes Care. 1998 Sep;21(9):1414-31.
• King H, Zimmet P. Trends in the prevalence and incidence of diabetes: non-insulin-dependent diabetes mellitus. World Health Stat Q. 1988;41(3-4):190-6.
• Lakka HM, Laaksonen DE, Lakka TA, Niskanen LK, Kumpusalo E, Tuomilehto J, Salonen JT. The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA. 2002 Dec 4;288(21):2709-16.
• Nilsson PM, Rööst M, Engström G, Hedblad B, Berglund G. Incidence of diabetes in middle-aged men is related to sleep disturbances. Diabetes Care. 2004 Oct;27(10):2464-9.
• Simon GE, VonKorff M. Prevalence, burden, and treatment of insomnia in primary care. Am J Psychiatry. 1997 Oct;154(10):1417-23.
• Spiegel K, Leproult R, Van Cauter E. Impact of sleep debt on metabolic and endocrine function. Lancet. 1999 Oct 23;354(9188):1435-9.
• Spiegel K, Tasali E, Penev P, Van Cauter E. Brief communication: Sleep curtailment in healthy young men is associated with decreased leptin levels, elevated ghrelin levels, and increased hunger and appetite. Ann Intern Med. 2004 Dec 7;141(11):846-50.
• Van Dongen HP, Maislin G, Mullington JM, Dinges DF. The cumulative cost of additional wakefulness: dose-response effects on neurobehavioral functions and sleep physiology from chronic sleep restriction and total sleep deprivation. Sleep. 2003 Mar 15;26(2):117-26. Erratum in: Sleep. 2004 Jun 15;27(4):600.

• Responsible Party: John W. Winkelman, MD, PhD, Associate Professor of Psychiatry, Brigham and Women's Hospital
• ClinicalTrials.gov Identifier: NCT00555750
• Other Study ID Numbers: BWH-HRC-2005-P-001997; ESRC0004; M01RR002635
• First Posted: Nov 9, 2007
• Last Update Posted: Dec 10, 2013
• Last Verified: Nov 1, 2013

• Keywords provided by John W. Winkelman, MD, PhD, Associate Professor of Psychiatry, Brigham and Women's Hospital: sleep; metabolism; insulin; glucose; actigraphy; diary; volumetry; GABA
• Additional relevant MeSH terms: Sleep Initiation and Maintenance Disorders; Eszopiclone

Study Results

Participant Flow

Arm/Group Title	Eszopiclone	Placebo
Arm/Group Description	nightly active medication (eszopiclone, 3 mg tablet) oral administration ~30 min before bed	nightly placebo (identical tablet to active medication) oral administration ~30 min before bed
Period Title: Overall Study
STARTED	10	10
COMPLETED	10	10
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Active	Placebo	Total
Arm/Group Description	active medication administration nightly before bed	nightly administration of placebo before bed	Total of all reporting groups
Overall Participants	10	10	20
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	10 100%	10 100%	20 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	2 20%	7 70%	9 45%
Male	8 80%	3 30%	11 55%
Region of Enrollment (participants) [Number]
United States	10 100%	10 100%	20 100%

Outcome Measures

1. Primary Outcome

Title	Change in Glucose Tolerance (Kg) in Response to Insulin-modified Intravenous Glucose Tolerance Test
Description	Difference in glucose tolerance (Kg) in response to insulin-modified intravenous glucose tolerance test. Glucose tolerance was calculated as the slope of the natural log of declining glucose values from minute 5 to minute 19 post-infusion. By convention, this negative slope is multiplied by -1, in other words, expressed as a rate of disposal.
Time Frame	baseline and 2 months post-treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active	Placebo
Arm/Group Description	active medication administration nightly before bed	nightly administration of placebo before bed
Measure Participants	10	10
Mean (Standard Deviation) [%/min, slope of natural log glucose]	.33 (.94)	-0.10 (.42)

2. Secondary Outcome

Title	Acute Insulin Response to Glucose (AIRg)
Description	Change over two months in 1st phase Insulin secretion
Time Frame	baseline and 2 months post-treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active	Placebo
Arm/Group Description	active medication administration nightly before bed	nightly administration of placebo before bed
Measure Participants	10	10
Mean (Standard Deviation) [mU*l^-1*min]	94.0 (269.0)	25.1 (74.7)

3. Secondary Outcome

Title	Change in Insulin Sensitivity (SI)
Description	Insulin sensitivity index (SI) "was defined in quantitative terms as the effect of insulin to catalyse the disappearance of glucose from plasma." [R. Bergman, Horm Res 2005;64(suppl 3):8-15]. SI calculated using Bergman's Minimal model analyses (Minmod Millennium 2000; R. Bergman, University of South- ern California, Los Angeles, CA)
Time Frame	baseline and 2 months post-treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active	Placebo
Arm/Group Description	active medication administration nightly before bed	nightly administration of placebo before bed
Measure Participants	10	10
Mean (Standard Deviation) [mU/l)^-1*min^-1]	-1.19 (2.57)	0.05 (3.43)

4. Secondary Outcome

Title	Change in Glucose Effectiveness (SG)
Description	Glucose effectiveness was defined as "the ability of glucose itself to enhance its own disappearance independent of an increment in insulin." [R. Bergman, Horm Res 2005;64(suppl 3):8-15]. SG calculated using Bergman's Minimal model analyses (Minmod Millennium 2000; R. Bergman, University of South- ern California, Los Angeles, CA)
Time Frame	baseline and 2 months post-treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active	Placebo
Arm/Group Description	active medication administration nightly before bed	nightly administration of placebo before bed
Measure Participants	10	10
Mean (Standard Deviation) [min^-1]	0.001 (0.004)	0.001 (0.009)

5. Secondary Outcome

Title	Change in HbA1c Levels
Description	Difference in HbA1c levels following two months treatment with eszopiclone versus placebo
Time Frame	baseline and 2 months post-treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active	Placebo
Arm/Group Description	active medication administration nightly before bed	nightly administration of placebo before bed
Measure Participants	10	10
Mean (Standard Error) [percentage of glycosylation]	.03 (.11)	-.09 (.06)

6. Secondary Outcome

Title	Pre-Treatment Leptin Levels
Description	Leptin Levels prior to two months treatment with eszopiclone or placebo, measure after an overnight fast
Time Frame	baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active	Placebo
Arm/Group Description	active medication administration nightly before bed	nightly administration of placebo before bed
Measure Participants	10	10
Mean (Standard Deviation) [ng/mL]	4.99 (3.63)	16.53 (11.37)

7. Secondary Outcome

Title	Post-treatment Leptin Levels
Description	Leptin levels following two months treatment with 3mg eszopiclone or placebo, measured after an overnight fast
Time Frame	two months post-treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active	Placebo
Arm/Group Description	active medication administration nightly before bed	nightly administration of placebo before bed
Measure Participants	9	10
Mean (Standard Deviation) [ng/mL]	5.49 (4.33)	15.28 (9.94)

8. Secondary Outcome

Title	Pre-treatment Ghrelin Levels
Description	Ghrelin levels prior to two months treatment with 3mg eszopiclone or placebo, measured after an overnight fast
Time Frame	baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active	Placebo
Arm/Group Description	active medication administration nightly before bed	nightly administration of placebo before bed
Measure Participants	10	10
Mean (Standard Deviation) [ng/mL]	573.14 (336.50)	648.41 (230.95)

9. Secondary Outcome

Title	Post-treatment Ghrelin Levels
Description	Ghrelin levels following two months treatment with 3mg eszopiclone or placebo, measured after an overnight fast
Time Frame	2 months post-treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active	Placebo
Arm/Group Description	active medication administration nightly before bed	nightly administration of placebo before bed
Measure Participants	9	10
Mean (Standard Deviation) [ng/mL]	544.95 (273.65)	670.94 (180.36)

10. Secondary Outcome

Title	Change in Subjective Sleepiness as Measured on the Karolinska Sleepiness Scale (KSS)
Description	At visits before and after two months treatment with 3mg eszopiclone or placebo, subjects completed a short test battery including the Karolinska Sleepiness Scale (KSS) every three hours during wake periods. KSS is a single-item scale of sleepiness on a scale from 1 ("very alert") to 9 ("very sleepy, fighting sleep, an effort to keep awake"). Subjective sleepiness was defined as mean deviation from baseline KSS.
Time Frame	baseline and 2 months post-treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active	Placebo
Arm/Group Description	active medication administration nightly before bed	nightly administration of placebo before bed
Measure Participants	10	10
Mean (Standard Error) [units on a scale]	0.53 (0.42)	0.38 (0.38)

11. Secondary Outcome

Title	Change in Mean Lapses of Attention
Description	At visits before and after two months treatment with 3mg eszopiclone or placebo, subjects completed a short test battery every three hours during wake periods. The battery included the Psychomotor Vigilance Task (PVT). The PVT involved a 10-minute visual reaction time (RT) performance test in which the subject was instructed to maintain the fastest possible RT to a simple visual stimulus. Lapses of attention refer to the number of times the subject failed to respond to the signal within 500ms. Mean lapses per test across 6 tests given a 4 hour intervals during normal waking hours (and not during the IVGTT) during the 30-hr were compared for the post-treatment visit as the absolute deviation from the baseline mean lapses/test.
Time Frame	baseline and 2 months post-treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active	Placebo
Arm/Group Description	active medication administration nightly before bed	nightly administration of placebo before bed
Measure Participants	10	10
Mean (Standard Error) [lapses of attention]	-0.04 (0.49)	0.07 (0.29)

12. Secondary Outcome

Title	Change in Total Sleep Time as Reported in Sleep Diaries
Description	Total sleep time reported on sleep diaries prior to treatment with 3mg eszopiclone or placebo. Change defined as baseline minus post-treatment).
Time Frame	baseline and 2 months post-treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active	Placebo
Arm/Group Description	active medication administration nightly before bed	nightly administration of placebo before bed
Measure Participants	9	10
Mean (Standard Deviation) [hours]	.58 (.36)	.09 (.01)

13. Secondary Outcome

Title	Change in Total Sleep Time Measured by PSG
Description	Change (baseline minus post-treatment) in total sleep time measured by polysomnography after two months treatment with 3mg eszopiclone or placebo
Time Frame	baseline and 2 months post-treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Active	Placebo
Arm/Group Description	active medication administration nightly before bed	nightly administration of placebo before bed
Measure Participants	10	10
Mean (Standard Deviation) [minutes]	2.9 (25.5)	-6.4 (30.2)

Adverse Events

Arm/Group Title	Active		Placebo
Arm/Group Description	active medication administration nightly before bed		nightly administration of placebo before bed
All Cause Mortality
	Active		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Active		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/10 (0%)
Other (Not Including Serious) Adverse Events
	Active		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/10 (100%)		10/10 (100%)
Cardiac disorders
Dizziness	3/10 (30%)	3	2/10 (20%)	3
Eye disorders
Eye irritation	1/10 (10%)	1	0/10 (0%)	0
Gastrointestinal disorders
Abdominal Discomfort	1/10 (10%)	3	2/10 (20%)	2
Constipation	1/10 (10%)	1	0/10 (0%)	0
Dry Mouth	2/10 (20%)	2	0/10 (0%)	0
Nausea	0/10 (0%)	0	1/10 (10%)	1
General disorders
Unpleasant Taste	4/10 (40%)	5	2/10 (20%)	2
Burning at infusion site	0/10 (0%)	0	1/10 (10%)	1
Feeling Hot	4/10 (40%)	5	6/10 (60%)	7
Headache	2/10 (20%)	3	5/10 (50%)	6
Puncture Site Pain	2/10 (20%)	2	3/10 (30%)	3
Injury, poisoning and procedural complications
Injection pressure sensation	0/10 (0%)	0	1/10 (10%)	1
Laceration	1/10 (10%)	1	0/10 (0%)	0
Vasovagal reaction	0/10 (0%)	0	1/10 (10%)	1
Vasovagal syncope	1/10 (10%)	1	0/10 (0%)	0
Venipuncture site bruising	1/10 (10%)	1	3/10 (30%)	4
Metabolism and nutrition disorders
Decreased appetite	0/10 (0%)	0	2/10 (20%)	3
Musculoskeletal and connective tissue disorders
Back Pain	1/10 (10%)	1	1/10 (10%)	1
Musculoskeletal pain	0/10 (0%)	0	2/10 (20%)	2
Pain in extremity	2/10 (20%)	2	2/10 (20%)	2
Plantar fasciitis	1/10 (10%)	1	0/10 (0%)	0
Nervous system disorders
Burning sensation	1/10 (10%)	3	0/10 (0%)	0
Paraesthesia	1/10 (10%)	1	3/10 (30%)	4
Psychiatric disorders
Nervousness	0/10 (0%)	0	1/10 (10%)	1
Somnolence	2/10 (20%)	2	2/10 (20%)	3
Reproductive system and breast disorders
Menstruation with increased bleeding	0/10 (0%)	0	1/10 (10%)	1
Respiratory, thoracic and mediastinal disorders
Respiratory tract infection	2/10 (20%)	2	2/10 (20%)	2
Skin and subcutaneous tissue disorders
Rash	1/10 (10%)	1	3/10 (30%)	4

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.