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

Study Overview
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Brief Summary
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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: A. 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. B. 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. C. 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

Detailed Description
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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.

Official Title
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The Attenuation of Second Generation Antipsychotic Induced Weight Gain in Adolescents and Adults Using Betahistine: A Double-Blind, Placebo-Controlled Trial

Conditions
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Bipolar I Disorder, Schizophrenia, Schizoaffective Disorder, Schizophreniform Disorder, Bipolar II, Bipolar NOS(Not Otherwise Specified), Psychotic Disorder Not Otherwise Specified, Autism Spectrum Disorder

Intervention / Treatment
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* Drug: Betahistine
* Drug: Placebo Oral Tablet


Participation Criteria
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Eligibility Criteria
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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: The patient has gained 7% of their weight since beginning of treatment with one or more of the current antipsychotics. The patient has had an increase of 7% of their weight during the last year while being treated with antipsychotics. 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. 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 59 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Body Mass Index (BMI) | Least Squares estimated change in BMI from end of study minus baseline | Measured at each visit from baseline to end of study over a 12 week period. | 
| Change in Waist Circumference | Least Squares estimated change in waist circumference from end of study minus baseline | Measured at each visit from baseline to end of study over a 12 week period. | 
| Change in Hip Circumference | Least Squares estimated change in hip circumference from end of study minus baseline | Measured at each visit from baseline to end of study over a 12 week period. | 
| Change in Glucose | Least Squares estimated change in glucose from end of study minus baseline | Measured at each visit from baseline to end of study over a 12 week period. | 
| Change in Cholesterol | Least Squares estimated change in cholesterol from end of study minus baseline | Measured at each visit from baseline to end of study over a 12 week period. | 
| Change in LDL | Least Squares estimated change in LDL from end of study minus baseline | Measured at each visit from baseline to end of study over a 12 week period. | 
| Change in HDL | Least Squares estimated change in HDL from end of study minus baseline | Measured at each visit from baseline to end of study over a 12 week period. | 
| Change in Triglycerides | Least Squares estimated change in triglycerides from end of study minus baseline | Measured at each visit from baseline to end of study over a 12 week period. | 
| Change in Appetite Hunger | 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. | Measured at baseline and 12 weeks | 
| Change in Appetite Fullness | 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. | .Measured at baseline and 12 weeks |