Inositol and Omega-3 Fatty Acids in Pediatric Mania

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT01396486
• Collaborator: (none)
• Enrollment: 69
• Location: 1
• Arms: 3
• Actual Duration (Months): 86.2
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief Summary

The purpose of this study is to a) evaluate the efficacy of omega-3 fatty acids versus inositol in the treatment of pediatric bipolar disorder, b) evaluate the efficacy of omega-3 fatty acid plus inositol in the treatment of pediatric bipolar disorder, and c) assess the side effect profile of omega-3 fatty acids plus inositol. This study will be a 12-week trial with children ages 5-12 years old with bipolar spectrum disorders.

Condition or Disease	Intervention/Treatment	Phase
Pediatric Bipolar Spectrum Disorders	Drug: Omega-3; Drug: Inositol	Phase 4

Detailed Description

The investigators propose to conduct a randomized, double blind, controlled trial that will evaluate effectiveness and tolerability of omega-3 fatty acids and inositol used alone and in combination. The investigators plan to decrease the variability in the population under study by limiting the age range to 5-12 years and excluding cases with significant, untreated, comorbidity. The cognitive effects/side effects with a neuropsychological battery pre and post treatment will be measured. Subjects with a history of failing treatment with two or more conventional treatments will be excluded.

This will be a 12-week, double-blind, randomized clinical trial study to compare efficacy and tolerability of the natural treatments omega-3 fatty acids and inositol used in combination in the treatment of bipolar spectrum disorders in children and adolescents (ages 5-12). Subjects will be randomized in double blind fashion to one of three arms: omega-3 fatty acids, inositol or the combined treatment. Further, the proposed study will include measures of cognition prior to starting study medication and at endpoint. The investigators will minimize the variability of the population under study by limiting the age range to 5-12 years, minimizing untreated or clinically significant comorbidity and excluding subjects who have already failed treatment with 2 or more anti-manic agents. Subjects will include youth ages 5-12 years with a bipolar spectrum disorder (type I, II, or NOS), mixed, manic, or hypomanic state, according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (American Psychiatric Association, 2000) (DSM-IV), randomized to 3 treatment arms: 1) treatment with omega-3 fatty acids (N=20); 2) treatment with inositol (N=20); 3) treatment with the combination of inositol and omega-3 fatty acids (N=20).

Study Design

• Study Type: Interventional
• Actual Enrollment: 69 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized Controlled Trial of Inositol and Omega-3 Fatty Acids in Pediatric Mania
• Actual Study Start Date: Feb 3, 2012
• Actual Primary Completion Date: Apr 11, 2019
• Actual Study Completion Date: Apr 11, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Omega-3/Placebo Combination Omega-3 and Placebo treatment.	Drug: Omega-3; Children with bipolar spectrum disorders ages 6-12 will receive treatment with omega-3 fatty acids. Study subjects may be randomized to receive 3000mg (6 500mg capsules) of omega-3 fatty acids for the duration of the study. Omega-3 fatty acid capsules are in the form of Nordic Naturals brand, ProOmega Junior, which contains 325mg EPA and 225mg DHA per two capsules.; Other Names: ProOmega Junior
Active Comparator: Placebo/Inositol Combination Placebo and Inositol treatment.	Drug: Inositol; Children with bipolar spectrum disorders ages 6-12 will receive treatment with inositol, omega-3 fatty acids, or both weekly for 12 weeks. Subjects weighing 25kg or more may be randomized to receive 2000mg (4 500mg capsules) of inositol (80mg/kg for a 25kg child). Children weighing less than 25kg will be dosed at 80mg/kg rounded down to the nearest thousand mg dose. Dosage will remain constant throughout the study.
Active Comparator: Omega-3/Inositol Combination Omega-3 and Inositol treatment.	Drug: Omega-3; Children with bipolar spectrum disorders ages 6-12 will receive treatment with omega-3 fatty acids. Study subjects may be randomized to receive 3000mg (6 500mg capsules) of omega-3 fatty acids for the duration of the study. Omega-3 fatty acid capsules are in the form of Nordic Naturals brand, ProOmega Junior, which contains 325mg EPA and 225mg DHA per two capsules.; Other Names: ProOmega Junior ; Drug: Inositol; Children with bipolar spectrum disorders ages 6-12 will receive treatment with inositol, omega-3 fatty acids, or both weekly for 12 weeks. Subjects weighing 25kg or more may be randomized to receive 2000mg (4 500mg capsules) of inositol (80mg/kg for a 25kg child). Children weighing less than 25kg will be dosed at 80mg/kg rounded down to the nearest thousand mg dose. Dosage will remain constant throughout the study.

Outcome Measures

Primary Outcome Measures

1. Improvement in Mania Symptoms by Change in Young Mania Rating Scale (YMRS) [Baseline to endpoint (12 weeks or last observation carried forward if dropped prior to week 12)]

   The Young Mania Rating Scale (YMRS) consists of 7 items rated on a scale from 0 (symptoms not present) to 4 (symptoms extremely severe) and 4 items rated on a scale from 0 (symptom not present) to 8 (symptom extremely severe).The YMRS score ranges from 0-60. Questions are asked about the last week. A higher score signifies more severe manic symptoms.

2. Improvement in Depression Symptoms by Children's Depression Rating Scale (CDRS) [Baseline to endpoint (12 weeks or last observation carried forward if dropped prior to week 12)]

   The Children's Depression Rating Scale (CDRS) is a clinician-rated instrument with 17 items scored on a 1 to 5 or 1 to 7 scale. A rating of 1 indicates normal, thus the minimum score is 17. The maximum score is 113. Scores of 20-30 suggest borderline depression. Scores of 40-60 indicate moderate depression.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 5 Years to 12 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Male or female subjects, 5-12 years of age.

2. Subjects must have a DSM-IV diagnosis of a bipolar spectrum disorder (type I, II, or Not Otherwise Specified (NOS)), and currently displaying mixed, manic, or hypomanic symptoms (without psychotic features) according to the DSM-IV based on clinical assessment and confirmed with structured diagnostic interview (Schedule of Affective Disorders and Schizophrenia for School-Age Children - Epidemiological Version (K-SADS-E)) (Orvaschel, 1994).

3. Subjects and their legal representative must have a level of understanding sufficient to communicate intelligently with the investigator and study coordinator, and to cooperate with all tests and examinations required by the protocol.

4. Subjects and their legal representative must be considered reliable.

5. Each subject and his/her authorized legal representative must understand the nature of the study. The subject's authorized legal representative must sign an informed consent document and the subject must sign an informed assent document.

6. Subjects must have an initial score on the YMRS total score of at least 20.

7. Subject must be able to swallow pills.

8. Subjects with ADHD and ODD will be allowed to participate in the study provided that the impairment associated with these disorders is of mild or moderate severity (not severe) and milder in severity relative to the impairment of the bipolar disorder, according to clinician evaluation. Subjects with comorbid anxiety disorders will be allowed to participate provided that the impairment associated with the anxiety is of minimal severity, according to clinician evaluation. Subjects with comorbid CD will be excluded.

Exclusion Criteria:

1. Investigator and his/her immediate family; defined as the investigator's spouse, parent, child, grandparent, or grandchild.

2. Serious or unstable illness including hepatic, renal, gastroenterological, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease.

3. History of bleeding diathesis, including those with von Willebrand disease.

4. Uncorrected hypothyroidism or hyperthyroidism.

5. History of sensitivity to omega-3 fatty acids or inositol. A non-responder or history of intolerance to omega-3 fatty acid or inositol, after 2 months of treatment at adequate doses as determined by the clinician.

6. Severe allergies or multiple adverse drug reactions.

7. Failed 2 or more previous trials with anti-manic treatments including lithium, anticonvulsants and atypical antipsychotic medication.

8. Current or past history of seizures.

9. DSM-IV substance use, abuse or dependence (unlikely in ages 5-12).

10. Judged clinically to be at serious suicidal risk.

11. Current diagnosis of schizophrenia.

12. Current diagnosis of conduct disorder

13. Pregnancy (unlikely in ages 5-12).

14. YMRS Item #8 (Content) score of 8 ("delusions; hallucinations").

15. YMRS total score above 40.

16. Girls who have begun menstruating.

17. C-SSRS score ≥ 4.

18. IQ < 70.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114

Sponsors and Collaborators

• Massachusetts General Hospital

Investigators

• Principal Investigator: Janet Wozniak, MD, Massachusetts General Hospital

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 2, 2018

More Information

Publications

None provided.

• Responsible Party: Janet Wozniak, MD, Assistant Professor of Psychiatry at Harvard Medical School and at Massachusetts General Hospital, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT01396486
• Other Study ID Numbers: 2009-P-001937
• First Posted: Jul 18, 2011
• Last Update Posted: Aug 13, 2020
• Last Verified: Aug 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Janet Wozniak, MD, Assistant Professor of Psychiatry at Harvard Medical School and at Massachusetts General Hospital, Massachusetts General Hospital: Omega-3 Fatty Acids; Fish Oil; Inositol; Natural supplements; Bipolar Spectrum Disorders; Mania; Depression; Children
• Additional relevant MeSH terms: Mania; Inositol

Study Results

Participant Flow

Pre-assignment Detail	While 69 subjects enrolled in the study, only 61 were randomized. Of the 8 subjects who enrolled but were not randomized, 3 were found ineligible, 3 withdrew, and 2 were lost to follow-up.

Arm/Group Title	Omega-3/Placebo	Placebo/Inositol	Omega-3/Inositol
Arm/Group Description	Combination Omega-3 and Placebo treatment. Omega-3: Children with bipolar spectrum disorders ages 6-12 will receive treatment with omega-3 fatty acids. Study subjects may be randomized to receive 3000mg (6 500mg capsules) of omega-3 fatty acids for the duration of the study. Omega-3 fatty acid capsules are in the form of Nordic Naturals brand, ProOmega Junior, which contains 325mg EPA and 225mg DHA per two capsules.	Combination Placebo and Inositol treatment. Inositol: Children with bipolar spectrum disorders ages 6-12 will receive treatment with inositol, omega-3 fatty acids, or both weekly for 12 weeks. Subjects weighing 25kg or more may be randomized to receive 2000mg (4 500mg capsules) of inositol (80mg/kg for a 25kg child). Children weighing less than 25kg will be dosed at 80mg/kg rounded down to the nearest thousand mg dose. Dosage will remain constant throughout the study.	Combination Omega-3 and Inositol treatment. Omega-3: Children with bipolar spectrum disorders ages 6-12 will receive treatment with omega-3 fatty acids. Study subjects may be randomized to receive 3000mg (6 500mg capsules) of omega-3 fatty acids for the duration of the study. Omega-3 fatty acid capsules are in the form of Nordic Naturals brand, ProOmega Junior, which contains 325mg EPA and 225mg DHA per two capsules. Inositol: Children with bipolar spectrum disorders ages 6-12 will receive treatment with inositol, omega-3 fatty acids, or both weekly for 12 weeks. Subjects weighing 25kg or more may be randomized to receive 2000mg (4 500mg capsules) of inositol (80mg/kg for a 25kg child). Children weighing less than 25kg will be dosed at 80mg/kg rounded down to the nearest thousand mg dose. Dosage will remain constant throughout the study.
Period Title: Overall Study
STARTED	20	19	22
Exposed	19	16	17
COMPLETED	10	7	10
NOT COMPLETED	10	12	12

Baseline Characteristics

Arm/Group Title	Omega-3/Placebo	Placebo/Inositol	Omega-3/Inositol	Total
Arm/Group Description	Combination Omega-3 and Placebo treatment. Omega-3: Children with bipolar spectrum disorders ages 6-12 will receive treatment with omega-3 fatty acids. Study subjects may be randomized to receive 3000mg (6 500mg capsules) of omega-3 fatty acids for the duration of the study. Omega-3 fatty acid capsules are in the form of Nordic Naturals brand, ProOmega Junior, which contains 325mg EPA and 225mg DHA per two capsules.	Combination Placebo and Inositol treatment. Inositol: Children with bipolar spectrum disorders ages 6-12 will receive treatment with inositol, omega-3 fatty acids, or both weekly for 12 weeks. Subjects weighing 25kg or more may be randomized to receive 2000mg (4 500mg capsules) of inositol (80mg/kg for a 25kg child). Children weighing less than 25kg will be dosed at 80mg/kg rounded down to the nearest thousand mg dose. Dosage will remain constant throughout the study.	Combination Omega-3 and Inositol treatment. Omega-3: Children with bipolar spectrum disorders ages 6-12 will receive treatment with omega-3 fatty acids. Study subjects may be randomized to receive 3000mg (6 500mg capsules) of omega-3 fatty acids for the duration of the study. Omega-3 fatty acid capsules are in the form of Nordic Naturals brand, ProOmega Junior, which contains 325mg EPA and 225mg DHA per two capsules. Inositol: Children with bipolar spectrum disorders ages 6-12 will receive treatment with inositol, omega-3 fatty acids, or both weekly for 12 weeks. Subjects weighing 25kg or more may be randomized to receive 2000mg (4 500mg capsules) of inositol (80mg/kg for a 25kg child). Children weighing less than 25kg will be dosed at 80mg/kg rounded down to the nearest thousand mg dose. Dosage will remain constant throughout the study.	Total of all reporting groups
Overall Participants	19	16	17	52
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	7.8 (1.6)	8.8 (2.3)	8.4 (2.5)	8.3 (2.2)
Sex: Female, Male (Count of Participants)
Female	8 42.1%	4 25%	8 47.1%	20 38.5%
Male	11 57.9%	12 75%	9 52.9%	32 61.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	4 21.1%	2 12.5%	0 0%	6 11.5%
Not Hispanic or Latino	14 73.7%	14 87.5%	17 100%	45 86.5%
Unknown or Not Reported	1 5.3%	0 0%	0 0%	1 1.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	1 6.3%	1 5.9%	2 3.8%
White	16 84.2%	14 87.5%	16 94.1%	46 88.5%
More than one race	1 5.3%	1 6.3%	0 0%	2 3.8%
Unknown or Not Reported	2 10.5%	0 0%	0 0%	2 3.8%
Region of Enrollment (participants) [Number]
United States	19 100%	16 100%	17 100%	52 100%
YMRS (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	26.1 (7.2)	25.8 (6.5)	24.2 (5.8)	25.4 (6.5)

Outcome Measures

1. Primary Outcome

Title	Improvement in Mania Symptoms by Change in Young Mania Rating Scale (YMRS)
Description	The Young Mania Rating Scale (YMRS) consists of 7 items rated on a scale from 0 (symptoms not present) to 4 (symptoms extremely severe) and 4 items rated on a scale from 0 (symptom not present) to 8 (symptom extremely severe).The YMRS score ranges from 0-60. Questions are asked about the last week. A higher score signifies more severe manic symptoms.
Time Frame	Baseline to endpoint (12 weeks or last observation carried forward if dropped prior to week 12)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Omega-3/Placebo	Placebo/Inositol	Omega-3/Inositol
Arm/Group Description	Combination Omega-3 and Placebo treatment. Omega-3: Children with bipolar spectrum disorders ages 6-12 will receive treatment with omega-3 fatty acids. Study subjects may be randomized to receive 3000mg (6 500mg capsules) of omega-3 fatty acids for the duration of the study. Omega-3 fatty acid capsules are in the form of Nordic Naturals brand, ProOmega Junior, which contains 325mg EPA and 225mg DHA per two capsules.	Combination Placebo and Inositol treatment. Inositol: Children with bipolar spectrum disorders ages 6-12 will receive treatment with inositol, omega-3 fatty acids, or both weekly for 12 weeks. Subjects weighing 25kg or more may be randomized to receive 2000mg (4 500mg capsules) of inositol (80mg/kg for a 25kg child). Children weighing less than 25kg will be dosed at 80mg/kg rounded down to the nearest thousand mg dose. Dosage will remain constant throughout the study.	Combination Omega-3 and Inositol treatment. Omega-3: Children with bipolar spectrum disorders ages 6-12 will receive treatment with omega-3 fatty acids. Study subjects may be randomized to receive 3000mg (6 500mg capsules) of omega-3 fatty acids for the duration of the study. Omega-3 fatty acid capsules are in the form of Nordic Naturals brand, ProOmega Junior, which contains 325mg EPA and 225mg DHA per two capsules. Inositol: Children with bipolar spectrum disorders ages 6-12 will receive treatment with inositol, omega-3 fatty acids, or both weekly for 12 weeks. Subjects weighing 25kg or more may be randomized to receive 2000mg (4 500mg capsules) of inositol (80mg/kg for a 25kg child). Children weighing less than 25kg will be dosed at 80mg/kg rounded down to the nearest thousand mg dose. Dosage will remain constant throughout the study.
Measure Participants	19	16	17
Mean (Standard Deviation) [units on a scale]	-4.8 (7.9)	-6.4 (6.4)	-10.2 (9.0)

2. Primary Outcome

Title	Improvement in Depression Symptoms by Children's Depression Rating Scale (CDRS)
Description	The Children's Depression Rating Scale (CDRS) is a clinician-rated instrument with 17 items scored on a 1 to 5 or 1 to 7 scale. A rating of 1 indicates normal, thus the minimum score is 17. The maximum score is 113. Scores of 20-30 suggest borderline depression. Scores of 40-60 indicate moderate depression.
Time Frame	Baseline to endpoint (12 weeks or last observation carried forward if dropped prior to week 12)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Omega-3/Placebo	Placebo/Inositol	Omega-3/Inositol
Arm/Group Description	Combination Omega-3 and Placebo treatment. Omega-3: Children with bipolar spectrum disorders ages 6-12 will receive treatment with omega-3 fatty acids. Study subjects may be randomized to receive 3000mg (6 500mg capsules) of omega-3 fatty acids for the duration of the study. Omega-3 fatty acid capsules are in the form of Nordic Naturals brand, ProOmega Junior, which contains 325mg EPA and 225mg DHA per two capsules.	Combination Placebo and Inositol treatment. Inositol: Children with bipolar spectrum disorders ages 6-12 will receive treatment with inositol, omega-3 fatty acids, or both weekly for 12 weeks. Subjects weighing 25kg or more may be randomized to receive 2000mg (4 500mg capsules) of inositol (80mg/kg for a 25kg child). Children weighing less than 25kg will be dosed at 80mg/kg rounded down to the nearest thousand mg dose. Dosage will remain constant throughout the study.	Combination Omega-3 and Inositol treatment. Omega-3: Children with bipolar spectrum disorders ages 6-12 will receive treatment with omega-3 fatty acids. Study subjects may be randomized to receive 3000mg (6 500mg capsules) of omega-3 fatty acids for the duration of the study. Omega-3 fatty acid capsules are in the form of Nordic Naturals brand, ProOmega Junior, which contains 325mg EPA and 225mg DHA per two capsules. Inositol: Children with bipolar spectrum disorders ages 6-12 will receive treatment with inositol, omega-3 fatty acids, or both weekly for 12 weeks. Subjects weighing 25kg or more may be randomized to receive 2000mg (4 500mg capsules) of inositol (80mg/kg for a 25kg child). Children weighing less than 25kg will be dosed at 80mg/kg rounded down to the nearest thousand mg dose. Dosage will remain constant throughout the study.
Measure Participants	19	16	17
Mean (Standard Deviation) [units on a scale]	-4.9 (10.6)	-5.6 (10.1)	-10.8 (7.4)

Adverse Events

Time Frame	12 weeks
Adverse Event Reporting Description	Consistent with good clinical practice, safety will be monitored by each subject's study clinician at each study visit. Subjects will be monitored by the study clinician for adverse events at each visit and adverse events will be recorded on an Adverse Events Form.
Arm/Group Title	Omega-3/Placebo		Placebo/Inositol		Omega-3/Inositol
Arm/Group Description	Combination Omega-3 and Placebo treatment. Omega-3: Children with bipolar spectrum disorders ages 6-12 will receive treatment with omega-3 fatty acids. Study subjects may be randomized to receive 3000mg (6 500mg capsules) of omega-3 fatty acids for the duration of the study. Omega-3 fatty acid capsules are in the form of Nordic Naturals brand, ProOmega Junior, which contains 325mg EPA and 225mg DHA per two capsules.		Combination Placebo and Inositol treatment. Inositol: Children with bipolar spectrum disorders ages 6-12 will receive treatment with inositol, omega-3 fatty acids, or both weekly for 12 weeks. Subjects weighing 25kg or more may be randomized to receive 2000mg (4 500mg capsules) of inositol (80mg/kg for a 25kg child). Children weighing less than 25kg will be dosed at 80mg/kg rounded down to the nearest thousand mg dose. Dosage will remain constant throughout the study.		Combination Omega-3 and Inositol treatment. Omega-3: Children with bipolar spectrum disorders ages 6-12 will receive treatment with omega-3 fatty acids. Study subjects may be randomized to receive 3000mg (6 500mg capsules) of omega-3 fatty acids for the duration of the study. Omega-3 fatty acid capsules are in the form of Nordic Naturals brand, ProOmega Junior, which contains 325mg EPA and 225mg DHA per two capsules. Inositol: Children with bipolar spectrum disorders ages 6-12 will receive treatment with inositol, omega-3 fatty acids, or both weekly for 12 weeks. Subjects weighing 25kg or more may be randomized to receive 2000mg (4 500mg capsules) of inositol (80mg/kg for a 25kg child). Children weighing less than 25kg will be dosed at 80mg/kg rounded down to the nearest thousand mg dose. Dosage will remain constant throughout the study.
All Cause Mortality
	Omega-3/Placebo		Placebo/Inositol		Omega-3/Inositol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/20 (0%)		0/19 (0%)		0/22 (0%)
Serious Adverse Events
	Omega-3/Placebo		Placebo/Inositol		Omega-3/Inositol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/20 (5%)		1/19 (5.3%)		0/22 (0%)
Psychiatric disorders
Agitated/Irritable	1/20 (5%)	1	1/19 (5.3%)	1	0/22 (0%)	0
Other (Not Including Serious) Adverse Events
	Omega-3/Placebo		Placebo/Inositol		Omega-3/Inositol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/20 (65%)		12/19 (63.2%)		10/22 (45.5%)
Ear and labyrinth disorders
Earache	0/20 (0%)		0/19 (0%)		1/22 (4.5%)
Gastrointestinal disorders
Nausea/Vomit/Diarrhea	4/20 (20%)		1/19 (5.3%)		3/22 (13.6%)
General disorders
Headache	0/20 (0%)		1/19 (5.3%)		1/22 (4.5%)
Increased Appetite	0/20 (0%)		2/19 (10.5%)		1/22 (4.5%)
Thirsty	0/20 (0%)		0/19 (0%)		1/22 (4.5%)
Dizzy/Lightheaded	0/20 (0%)		0/19 (0%)		1/22 (4.5%)
Bet Wetting	1/20 (5%)		0/19 (0%)		0/22 (0%)
Irregular Behavior	1/20 (5%)		0/19 (0%)		0/22 (0%)
Weight Gain	0/20 (0%)		1/19 (5.3%)		0/22 (0%)
Chewing Inside of Cheek	0/20 (0%)		1/19 (5.3%)		0/22 (0%)
Infections and infestations
Cold/Infection/Allergy	3/20 (15%)		1/19 (5.3%)		1/22 (4.5%)
Strep Throat	1/20 (5%)		0/19 (0%)		0/22 (0%)
Injury, poisoning and procedural complications
Scrape	1/20 (5%)		0/19 (0%)		0/22 (0%)
Musculoskeletal and connective tissue disorders
Musculoskeletal	0/20 (0%)		0/19 (0%)		1/22 (4.5%)
Nervous system disorders
Insomnia	0/20 (0%)		1/19 (5.3%)		1/22 (4.5%)
Sedation	0/20 (0%)		1/19 (5.3%)		0/22 (0%)
Neurological	0/20 (0%)		0/19 (0%)		1/22 (4.5%)
Autonomic	0/20 (0%)		0/19 (0%)		1/22 (4.5%)
Sleep Walking	0/20 (0%)		1/19 (5.3%)		0/22 (0%)
Psychiatric disorders
Agitated/Irritable	1/20 (5%)		2/19 (10.5%)		0/22 (0%)
Tics	0/20 (0%)		0/19 (0%)		1/22 (4.5%)
Psychotic Episode	0/20 (0%)		1/19 (5.3%)		0/22 (0%)
Agitated with Homicidal Statements	0/20 (0%)		0/19 (0%)		1/22 (4.5%)
Respiratory, thoracic and mediastinal disorders
Pulmonary	0/20 (0%)		0/19 (0%)		1/22 (4.5%)
Skin and subcutaneous tissue disorders
Dermatological	1/20 (5%)		0/19 (0%)		0/22 (0%)

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.