Efficacy and Tolerability Study of Betahistine to Ameliorate Antipsychotic Associated Weight Gain

• Sponsor: Nathan Kline Institute for Psychiatric Research (Other)
• Overall Status: Completed
• CT.gov ID: NCT00709202
• Collaborator: Stanley Medical Research Institute (Other)
• Enrollment: 48
• Location: 1
• Arms: 2
• Duration (Months): 101
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The study attempts to evaluate a histamine analog long used for the treatment of Meniere's disease, betahistine, that shows promise in reversing the antihistaminergic effects thought to be involved in antipsychotic induced weight gain.

Hypothesis to be tested:

1. Patients who have gained a developmentally inappropriate amount of weight on antipsychotics (AP) will see their weight and BMI decrease with betahistine augmentation as compared to placebo augmentation.

2. Betahistine augmentation in AP treated patients will increase levels of satiety in a standardized meal situation and decrease caloric intake as compared to placebo augmentation.

3. Metabolic effects of betahistine augmentation in AP treated patients will be reflected in differences in waist circumference, hip circumference and waist hip ratios D. Betahistine augmentation in this population will lead to decrease in fasting glucose-lipid lab values related to the development of metabolic syndrome as compared to placebo augmentation

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia; Schizoaffective Disorder; Schizophreniform Disorder; Bipolar I Disorder; Bipolar II; Bipolar NOS(Not Otherwise Specified); Psychotic Disorder Not Otherwise Specified; Autism Spectrum Disorder	Drug: Betahistine; Drug: Placebo Oral Tablet	Phase 2

Detailed Description

Subjects for this study were adolescents and adults from age 12 to age 59. Subjects were individuals who have been psychiatrically stabilized on first or second generation antipsychotic medication, and have gained substantial weight during their treatment. Subjects were excluded if they have asthma, peptic ulcer disease (diseases which may be exacerbated by a histamine analog) or are prescribed medications known to affect body composition or metabolism other than those currently being studied. Subjects were randomized to receive either betahistine or placebo at a 1:1 ratio.

Study Design

• Study Type: Interventional
• Actual Enrollment: 48 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: The Attenuation of Second Generation Antipsychotic Induced Weight Gain in Adolescents and Adults Using Betahistine: A Double-Blind, Placebo-Controlled Trial
• Study Start Date: Jul 1, 2008
• Actual Primary Completion Date: May 1, 2016
• Actual Study Completion Date: Dec 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 1 Subjects assigned to this arm will receive Betahistine.	Drug: Betahistine; Subjects will be started on 8 mg BID of Betahistine and titrated up to 24 mg BID (BID = 2 times a day)..; Other Names: Serc, Betaserc, Betaserk
Placebo Comparator: 2 Subjects in this group will received placebo.	Drug: Placebo Oral Tablet

Outcome Measures

Primary Outcome Measures

1. Change in Weight [Measured at each visit from baseline to end of study over a 12 week period]

   Least Squares estimated change in weight from end of study minus baseline

Secondary Outcome Measures

1. Change in Body Mass Index (BMI) [Measured at each visit from baseline to end of study over a 12 week period.]

   Least Squares estimated change in BMI from end of study minus baseline

2. Change in Waist Circumference [Measured at each visit from baseline to end of study over a 12 week period.]

   Least Squares estimated change in waist circumference from end of study minus baseline

3. Change in Hip Circumference [Measured at each visit from baseline to end of study over a 12 week period.]

   Least Squares estimated change in hip circumference from end of study minus baseline

4. Change in Glucose [Measured at each visit from baseline to end of study over a 12 week period.]

   Least Squares estimated change in glucose from end of study minus baseline

5. Change in Cholesterol [Measured at each visit from baseline to end of study over a 12 week period.]

   Least Squares estimated change in cholesterol from end of study minus baseline

6. Change in LDL [Measured at each visit from baseline to end of study over a 12 week period.]

   Least Squares estimated change in LDL from end of study minus baseline

7. Change in HDL [Measured at each visit from baseline to end of study over a 12 week period.]

   Least Squares estimated change in HDL from end of study minus baseline

8. Change in Triglycerides [Measured at each visit from baseline to end of study over a 12 week period.]

   Least Squares estimated change in triglycerides from end of study minus baseline

9. Change in Appetite Hunger [Measured at baseline and 12 weeks]

   Least Squares estimated change in appetite hunger from end of study minus baseline.The scale used has no specific name. It is a Visual Analogue Scale, where a line is drawn of 10 cm long with the statement beneath the line" How Hungry do you feel '. The subject places an X on the line. The measurements, the number of centimeters from the start of the line ("O"), indicate the amount of hunger. The higher the cm number the higher the feeling of hunger. The measure reported is the difference in this scale reading in cm from after the test meal to before consuming the test meal. The number (mean, s.e.m) presented is the analysis of covariance model estimated difference score at the end of study, with the covariate of the same score at baseline.

10. Change in Appetite Fullness [.Measured at baseline and 12 weeks]

    Least Squares estimated change in appetite fullness from end of study minus baseline.The scale used has no specific name. It is a Visual Analogue Scale, where a line is drawn of 10 cm long with the statement beneath the line" How full do you feel '. The subject places an X on the line. The measurements, the number of centimeters from the start of the line ("O"). indicate amount of feeling of fullness. The higher the cm number the higher the feeling of fullness. The measure reported is the difference in this scale reading in cm from after the test meal to before consuming the test meal. The number (mean, s.e.m.) presented is the analysis of covariance model estimated difference score at the end of study, with the covariate of the same score at baseline.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 59 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Adolescents and Adults ages 12-59 with a diagnosis of Schizophrenia, Schizoaffective Disorder, Schizophreniform, Bipolar I, Bipolar II, Bipolar NOS or Psychotic Disorder NOS, Autism Spectrum Disorder

• Patients will be currently treated with antipsychotics

Patients will qualify for entry if they meet the following weight criteria:

1. The patient has gained 7% of their weight since beginning of treatment with one or more of the current antipsychotics.

2. The patient has had an increase of 7% of their weight during the last year while being treated with antipsychotics.

3. The patient has a BMI of 30 or more and has gained 10 lbs or more in the past 8 months while being treated with antipsychotic medications.

4. The patient has a BMI of 35 or greater at the current time, and his chart shows a history of consistent weight gain over the past 1 to 3 years during treatment with antipsychotics.

.

Exclusion Criteria:

• Subjects will be excluded if they have asthma, peptic ulcer disease (diseases which may be exacerbated by a histamine analog), or history of pheochromocytoma or peptic ulcer disease. Patients will be excluded if they are prescribed medications known to affect body weight or glucose-lipid metabolism, such as prescription or over the counter medications taken for the purpose of weight reduction. Subjects who are currently treated with metformin, for less than 6 months and have shown recent weight change on metformin. Patients on thyroid replacement therapy or lipid-lowering agents whose dosage has changed by more than 50 % in the past month will be excluded. If they are relatively stable doses of these medications they will not be excluded. Patients who are on lipid lowering medication, thyroid replacement medication, or diabetes medication, (excluding metformin), must remain on these medications throughout the period of the study. Females who are pregnant or breast feeding will be excluded.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Nathan Kline Insitute for Psychiatric Research	Orangeburg	New York	United States	10962

Sponsors and Collaborators

• Nathan Kline Institute for Psychiatric Research
• Stanley Medical Research Institute

Investigators

• Principal Investigator: Robert C Smith, M.D., Nathan Kline Institute for Psychiatric Research

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Robert C. Smith MD PhD, Research Psychiatrist, Research Professor of Psychiatry, Nathan Kline Institute for Psychiatric Research
• ClinicalTrials.gov Identifier: NCT00709202
• Other Study ID Numbers: 07TGF-1112
• First Posted: Jul 3, 2008
• Last Update Posted: Jan 25, 2019
• Last Verified: Jan 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Disease; Weight Gain; Schizophrenia; Autism Spectrum Disorder; Mental Disorders; Psychotic Disorders; Betahistine

Study Results

Participant Flow

Pre-assignment Detail	48 subjects signed consent for the study. 8 subjects withdrew consent before randomization and another subject withdrew before the first post-baseline measurement. Therefore, only 39 subjects were analyzed.

Arm/Group Title	Betahistine	Placebo
Arm/Group Description	Subjects assigned to this arm will receive Betahistine. Betahistine: Subjects will be started on 8 mg BID of Betahistine and titrated up to 24 mg BID.	Subjects in this group will received placebo. Placebo: Subjects will be receive placebo tablets matched in number to betahistine tablets
Period Title: Overall Study
STARTED	19	21
COMPLETED	13	15
NOT COMPLETED	6	6

Baseline Characteristics

Arm/Group Title	Betahistine	Placebo	Total
Arm/Group Description	Subjects assigned to this arm will receive Betahistine. Betahistine: Subjects will be started on 8 mg BID of Betahistine and titrated up to 24 mg BID.	Subjects in this group will received placebo. Betahistine: Subjects will be started on 8 mg BID of Betahistine and titrated up to 24 mg BID.	Total of all reporting groups
Overall Participants	19	20	39
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	31.1 (14.9)	31.1 (14.0)	31.1 (14.2)
Sex: Female, Male (Count of Participants)
Female	12 63.2%	11 55%	23 59%
Male	7 36.8%	9 45%	16 41%
Race/Ethnicity, Customized (Count of Participants)
White-Caucasian	4 21.1%	9 45%	13 33.3%
Black-African American	7 36.8%	7 35%	14 35.9%
Hispanic	4 21.1%	4 20%	8 20.5%
Other	4 21.1%	0 0%	4 10.3%
Region of Enrollment (participants) [Number]
United States	19 100%	20 100%	39 100%

Outcome Measures

1. Primary Outcome

Title	Change in Weight
Description	Least Squares estimated change in weight from end of study minus baseline
Time Frame	Measured at each visit from baseline to end of study over a 12 week period

Outcome Measure Data

Analysis Population Description

Least Squares estimated change in weight from end of study minus baseline for all subjects who had at least one post-baseline weight evaluation, using mixed model analysis.

Arm/Group Title	Betahistine	Placebo
Arm/Group Description	Subjects assigned to this arm will receive Betahistine. Betahistine: Subjects will be started on 8 mg BID of Betahistine and titrated up to 24 mg BID.	Subjects in this group will received placebo. Placebo Oral Tablet
Measure Participants	19	20
Least Squares Mean (Standard Error) [kg. (killograms)]	-2.0021 (0.7970)	-1.5490 (0.7650)

2. Secondary Outcome

Title	Change in Body Mass Index (BMI)
Description	Least Squares estimated change in BMI from end of study minus baseline
Time Frame	Measured at each visit from baseline to end of study over a 12 week period.

Outcome Measure Data

Analysis Population Description

Least Squares estimated change in BMI from end of study minus baseline for all subjects who had at least one post-baseline weight evaluation, using mixed model analysis.

Arm/Group Title	Betahistine	Placebo
Arm/Group Description	Subjects assigned to this arm will receive Betahistine. Betahistine: Subjects will be started on 8 mg BID of Betahistine and titrated up to 24 mg BID.	Subjects in this group will received placebo. Placebo Oral Tablet
Measure Participants	19	20
Least Squares Mean (Standard Error) [kg/m^2]	-0.5524 (0.2747)	-0.5637 (0.2653)

3. Secondary Outcome

Title	Change in Waist Circumference
Description	Least Squares estimated change in waist circumference from end of study minus baseline
Time Frame	Measured at each visit from baseline to end of study over a 12 week period.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Betahistine	Placebo
Arm/Group Description	Subjects assigned to this arm will receive Betahistine. Betahistine: Subjects will be started on 8 mg BID of Betahistine and titrated up to 24 mg BID.	Subjects in this group will received placebo. Placebo: Subjects will be receive placebo tablets matched in number to betahistine tablets
Measure Participants	19	20
Least Squares Mean (Standard Error) [centimeters]	4.0928 (1.3884)	2.4864 (1.3669)

4. Secondary Outcome

Title	Change in Hip Circumference
Description	Least Squares estimated change in hip circumference from end of study minus baseline
Time Frame	Measured at each visit from baseline to end of study over a 12 week period.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Betahistine	Placebo
Arm/Group Description	Subjects assigned to this arm will receive Betahistine. Betahistine: Subjects will be started on 8 mg BID of Betahistine and titrated up to 24 mg BID.	Subjects in this group will received placebo. Placebo: Subjects will be receive placebo tablets matched in number to betahistine tablets
Measure Participants	19	20
Least Squares Mean (Standard Error) [centimeters]	1.7957 (1.3837)	1.3668 (1.3118)

5. Secondary Outcome

Title	Change in Glucose
Description	Least Squares estimated change in glucose from end of study minus baseline
Time Frame	Measured at each visit from baseline to end of study over a 12 week period.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Betahistine	Placebo
Arm/Group Description	Subjects assigned to this arm will receive Betahistine. Betahistine: Subjects will be started on 8 mg BID of Betahistine and titrated up to 24 mg BID.	Subjects in this group will received placebo. Placebo: Subjects will be receive placebo tablets matched in number to betahistine tablets
Measure Participants	14	14
Least Squares Mean (Standard Error) [mg/dL]	4.292 (2.116)	3.136 (2.116)

6. Secondary Outcome

Title	Change in Cholesterol
Description	Least Squares estimated change in cholesterol from end of study minus baseline
Time Frame	Measured at each visit from baseline to end of study over a 12 week period.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Betahistine	Placebo
Arm/Group Description	Subjects assigned to this arm will receive Betahistine. Betahistine: Subjects will be started on 8 mg BID of Betahistine and titrated up to 24 mg BID.	Subjects in this group will received placebo. Placebo: Subjects will be receive placebo tablets matched in number to betahistine tablets
Measure Participants	14	14
Least Squares Mean (Standard Error) [mg/dL]	1.087 (0.079)	1.010 (0.079)

7. Secondary Outcome

Title	Change in LDL
Description	Least Squares estimated change in LDL from end of study minus baseline
Time Frame	Measured at each visit from baseline to end of study over a 12 week period.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Betahistine	Placebo
Arm/Group Description	Subjects assigned to this arm will receive Betahistine. Betahistine: Subjects will be started on 8 mg BID of Betahistine and titrated up to 24 mg BID.	Subjects in this group will received placebo. Placebo: Subjects will be receive placebo tablets matched in number to betahistine tablets
Measure Participants	14	14
Least Squares Mean (Standard Error) [mg/dL]	1.799 (6.633)	0.915 (6.633)

8. Secondary Outcome

Title	Change in HDL
Description	Least Squares estimated change in HDL from end of study minus baseline
Time Frame	Measured at each visit from baseline to end of study over a 12 week period.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Betahistine	Placebo
Arm/Group Description	Subjects assigned to this arm will receive Betahistine. Betahistine: Subjects will be started on 8 mg BID of Betahistine and titrated up to 24 mg BID.	Subjects in this group will received placebo. Placebo: Subjects will be receive placebo tablets matched in number to betahistine tablets
Measure Participants	14	14
Least Squares Mean (Standard Error) [mg/dL]	2.555 (1.815)	-0.840 (1.815)

9. Secondary Outcome

Title	Change in Triglycerides
Description	Least Squares estimated change in triglycerides from end of study minus baseline
Time Frame	Measured at each visit from baseline to end of study over a 12 week period.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Betahistine	Placebo
Arm/Group Description	Subjects assigned to this arm will receive Betahistine. Betahistine: Subjects will be started on 8 mg BID of Betahistine and titrated up to 24 mg BID.	Subjects in this group will received placebo. Placebo: Subjects will be receive placebo tablets matched in number to betahistine tablets
Measure Participants	14	14
Least Squares Mean (Standard Error) [mg/dL]	-4.426 (11.119)	-3.360 (11.119)

10. Secondary Outcome

Title	Change in Appetite Hunger
Description	Least Squares estimated change in appetite hunger from end of study minus baseline.The scale used has no specific name. It is a Visual Analogue Scale, where a line is drawn of 10 cm long with the statement beneath the line" How Hungry do you feel '. The subject places an X on the line. The measurements, the number of centimeters from the start of the line ("O"), indicate the amount of hunger. The higher the cm number the higher the feeling of hunger. The measure reported is the difference in this scale reading in cm from after the test meal to before consuming the test meal. The number (mean, s.e.m) presented is the analysis of covariance model estimated difference score at the end of study, with the covariate of the same score at baseline.
Time Frame	Measured at baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Betahistine	Placebo
Arm/Group Description	Subjects assigned to this arm will receive Betahistine. Betahistine: Subjects will be started on 8 mg BID of Betahistine and titrated up to 24 mg BID.	Subjects in this group will received placebo. Placebo: Subjects will be receive placebo tablets matched in number to betahistine tablets
Measure Participants	14	17
Least Squares Mean (Standard Error) [units on a scale]	-3.605 (.896)	-3.684 (.813)

11. Secondary Outcome

Title	Change in Appetite Fullness
Description	Least Squares estimated change in appetite fullness from end of study minus baseline.The scale used has no specific name. It is a Visual Analogue Scale, where a line is drawn of 10 cm long with the statement beneath the line" How full do you feel '. The subject places an X on the line. The measurements, the number of centimeters from the start of the line ("O"). indicate amount of feeling of fullness. The higher the cm number the higher the feeling of fullness. The measure reported is the difference in this scale reading in cm from after the test meal to before consuming the test meal. The number (mean, s.e.m.) presented is the analysis of covariance model estimated difference score at the end of study, with the covariate of the same score at baseline.
Time Frame	.Measured at baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Betahistine	Placebo
Arm/Group Description	Subjects assigned to this arm will receive Betahistine. Betahistine: Subjects will be started on 8 mg BID of Betahistine and titrated up to 24 mg BID.	Subjects in this group will received placebo. Placebo: Subjects will be receive placebo tablets matched in number to betahistine tablets
Measure Participants	13	17
Least Squares Mean (Standard Error) [units on a scale]	1.800 (1.058)	4.698 (.925)

Adverse Events

Time Frame	12 weeks during study drug administration
Adverse Event Reporting Description	We are reporting adverse events reported to IRB (Institutional Review Board) on adverse event forms.
Arm/Group Title	Betahistine		Placebo
Arm/Group Description	Subjects assigned to this arm will receive Betahistine. Betahistine: Subjects will be started on 8 mg BID of Betahistine and titrated up to 24 mg BID.		Subjects in this group will received placebo. Placebo Oral Tablet
All Cause Mortality
	Betahistine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/19 (0%)		0/20 (0%)
Serious Adverse Events
	Betahistine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/19 (0%)		0/20 (0%)
Other (Not Including Serious) Adverse Events
	Betahistine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/19 (10.5%)		4/20 (20%)
Cardiac disorders
chest pain	0/19 (0%)	0	1/20 (5%)	1
Eye disorders
conjunctivitis	1/19 (5.3%)	1	0/20 (0%)	0
Gastrointestinal disorders
Vomiting	1/19 (5.3%)	1	0/20 (0%)	0
Psychiatric disorders
chest pain	0/19 (0%)	0	1/20 (5%)	1
Increase in level of psychiatric symptoms	0/19 (0%)	0	1/20 (5%)	1
Skin and subcutaneous tissue disorders
skin rash	0/19 (0%)	0	1/20 (5%)	1

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.