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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00709202

Enrollment

Registered

2008-07-03

Start date

2008-07-31

Completion date

2016-12-31

Last updated

2019-01-25

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

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

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.

Interventions

DRUGPlacebo Oral Tablet

DRUGBetahistine

Subjects will be started on 8 mg BID of Betahistine and titrated up to 24 mg BID (BID = 2 times a day)..

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 59 Years

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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
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
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
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
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
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
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
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.
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.
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

Countries

United States

Participant flow

Pre-assignment details

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.

Participants by arm

Arm	Count
Betahistine 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.	19
Placebo 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.	20
Total	39

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Withdrawal by Subject	6	6

Baseline characteristics

Characteristic	Betahistine	Placebo	Total
Age, Continuous	31.1 years STANDARD_DEVIATION 14.9	31.1 years STANDARD_DEVIATION 14	31.1 years STANDARD_DEVIATION 14.2
Race/Ethnicity, Customized Race-Ethnicity Black-African American	7 Participants	7 Participants	14 Participants
Race/Ethnicity, Customized Race-Ethnicity Hispanic	4 Participants	4 Participants	8 Participants
Race/Ethnicity, Customized Race-Ethnicity Other	4 Participants	0 Participants	4 Participants
Race/Ethnicity, Customized Race-Ethnicity White-Caucasian	4 Participants	9 Participants	13 Participants
Region of Enrollment United States	19 participants	20 participants	39 participants
Sex: Female, Male Female	12 Participants	11 Participants	23 Participants
Sex: Female, Male Male	7 Participants	9 Participants	16 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 19	0 / 20
other Total, other adverse events	2 / 19	4 / 20
serious Total, serious adverse events	0 / 19	0 / 20

Outcome results

Primary

Change in Weight

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

Population: 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	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Betahistine	Change in Weight	-2.0021 kg. (killograms)	Standard Error 0.797
Placebo	Change in Weight	-1.5490 kg. (killograms)	Standard Error 0.765

Secondary

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.

Time frame: .Measured at baseline and 12 weeks

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Betahistine	Change in Appetite Fullness	1.800 units on a scale	Standard Error 1.058
Placebo	Change in Appetite Fullness	4.698 units on a scale	Standard Error 0.925

Secondary

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.

Time frame: Measured at baseline and 12 weeks

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Betahistine	Change in Appetite Hunger	-3.605 units on a scale	Standard Error 0.896
Placebo	Change in Appetite Hunger	-3.684 units on a scale	Standard Error 0.813

Secondary