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

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

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

Study Overview

• Status: Completed
• Conditions: Schizophrenia; Schizoaffective Disorder; Schizophreniform Disorder; Autism Spectrum Disorder; Bipolar I Disorder; Psychotic Disorder Not Otherwise Specified; Bipolar II; Bipolar NOS(Not Otherwise Specified)
• Intervention / Treatment: Drug: Placebo Oral Tablet; Drug: Betahistine

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 Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • Orangeburg, New York, United States, 10962
      • Nathan Kline Insitute for Psychiatric Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 59 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Nathan Kline Institute for Psychiatric Research
• Collaborators: Stanley Medical Research Institute
• Investigators: Principal Investigator: Robert C Smith, M.D., Nathan Kline Institute for Psychiatric Research

Publications and helpful links

General Publications

• Kang D, Jing Z, Li R, Hei G, Shao T, Li L, Sun M, Yang Y, Wang Y, Wang X, Long Y, Huang X, Wu R. Effect of Betahistine and Metformin on Antipsychotic-Induced Weight Gain: An Analysis of Two Clinical Trials. Front Psychiatry. 2018 Nov 27;9:620. doi: 10.3389/fpsyt.2018.00620. eCollection 2018.

Study record dates

Study Major Dates

• Study Start: July 1, 2008
• Primary Completion (ACTUAL): May 1, 2016
• Study Completion (ACTUAL): December 1, 2016

Study Registration Dates

• First Submitted: July 1, 2008
• First Submitted That Met QC Criteria: July 2, 2008
• First Posted (ESTIMATE): July 3, 2008

Study Record Updates

• Last Update Posted (ACTUAL): January 25, 2019
• Last Update Submitted That Met QC Criteria: January 20, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Body Weight; Schizophrenia Spectrum and Other Psychotic Disorders; Body Weight Changes; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Schizophrenia; Disease; Psychotic Disorders; Mental Disorders; Autism Spectrum Disorder; Weight Gain; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Histamine Agents; Histamine Agonists; Betahistine
• Other Study ID Numbers: 07TGF-1112

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO