Clinical trial NCT00709202: Efficacy and Tolerability Study of Betahistine to Ameliorate Antipsychotic Associated Weight Gain
Official title: The Attenuation of Second Generation Antipsychotic Induced Weight Gain in Adolescents and Adults Using Betahistine: A Double-Blind, Placebo-Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Schizophrenia
Schizoaffective Disorder
Schizophreniform Disorder
Bipolar I Disorder
Bipolar II
Bipolar NOS(Not Otherwise Specified)
Psychotic Disorder Not Otherwise Specified
Autism Spectrum Disorder
Lead sponsor: Nathan Kline Institute for Psychiatric Research
Sponsor class: OTHER
Collaborators: name: Stanley Medical Research Institute
First posted: 2008-07-03
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 59
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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:

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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in Weight
timeFrame: Measured at each visit from baseline to end of study over a 12 week period
Secondary outcomes:
measure: Change in Body Mass Index (BMI)
timeFrame: Measured at each visit from baseline to end of study over a 12 week period.
measure: Change in Waist Circumference
timeFrame: Measured at each visit from baseline to end of study over a 12 week period.
measure: Change in Hip Circumference
timeFrame: Measured at each visit from baseline to end of study over a 12 week period.
measure: Change in Glucose
timeFrame: Measured at each visit from baseline to end of study over a 12 week period.
measure: Change in Cholesterol
timeFrame: Measured at each visit from baseline to end of study over a 12 week period.
measure: Change in LDL
timeFrame: Measured at each visit from baseline to end of study over a 12 week period.
measure: Change in HDL
timeFrame: Measured at each visit from baseline to end of study over a 12 week period.
measure: Change in Triglycerides
timeFrame: Measured at each visit from baseline to end of study over a 12 week period.
measure: Change in Appetite Hunger
timeFrame: Measured at baseline and 12 weeks
measure: Change in Appetite Fullness
timeFrame: .Measured at baseline and 12 weeks
Other outcomes:
Locations:
city: Orangeburg
country: United States
facility: Nathan Kline Insitute for Psychiatric Research
state: New York
Study officials:
affiliation: Nathan Kline Institute for Psychiatric Research
name: Robert C Smith, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.