Clinical trial NCT00409305: The Effect of Betahistine on Body Weight in Obese Subjects
Official title: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Examine the Effect of Betahistine on Body Weight in Obese Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Obesity
Lead sponsor: OBEcure Ltd.
Sponsor class: INDUSTRY
First posted: 2006-12-08
Enrollment: 280
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to examine the effect that betahistine has on body weight in obese subjects.


Eligibility criteria: Inclusion Criteria:

* Signed written informed consent;
* Male or female subjects 18 to 65 years of age;
* Is obese with a BMI greater than or equal to 30 kg/m2 to less than or equal to 40 kg/m2;
* Has been obese for at least 1 year prior to screening; and
* If female, is nonlactating, has a negative urine pregnancy test result, and does not plan on becoming pregnant during the study, or not of childbearing potential (hysterectomy or tubal ligation at least 6 months prior to randomization or post-menopausal for 1 year); if of childbearing potential (including peri-menopausal women who have had a menstrual period within 1 year) must practice or be willing to continue to practice appropriate birth control (such as implants, injectables, oral contraceptives, some intrauterine contraceptive devices, sexual abstinence, tubal ligation, or a vasectomized partner) during the entire study duration.

Exclusion Criteria:

* Has obesity of known endocrine origin (e.g., Cushing's disease, Addison's disease, hypothalamic tumor);
* Has a medical history (e.g., morbid childhood obesity) and/or physical characteristics (e.g., polydactyly) suggestive of genetic obesity (e.g., ob/ob genotype) or syndromatic obesity (e.g., Prader-Willi syndrome, Bardet Biedl syndrome);
* Previous surgical procedures for weight loss;
* Has had liposuction within 1 year before screening or is planning to have liposuction during the study;
* History of bulimia or evidence of laxative abuse;
* Has had a body weight loss of \>4 kg in the 90 days prior to screening;
* Has taken drugs capable of influencing body weight 30 days prior to screening;
* Has recently started or plans on starting a smoking cessation program;
* Has had a major change in daily physical activity (e.g., initiation of an exercise program) or started a weight loss program within 90 days prior to screening;
* Is unwilling or unable to participate in a dietary program as part of the study;
* Is \<80% compliant with study medication in the single-blind placebo run-in period;
* Has a clinically significant history or presence of any of the following conditions:
* Active or past history of cardiovascular or cerebrovascular disease including unstable angina, myocardial infarction, transient ischemic attacks/stroke, clinically significant arrhythmia, congestive heart failure, or cardiac valve abnormalities;
* Liver disease (irrespective of transaminase concentrations);
* Pheochromocytoma;
* Porphyria;
* Type 1 diabetes mellitus;
* Type 2 diabetes mellitus on treatment other than metformin monotherapy and/or diet with HbA1c less than or equal to 8%;
* Severe type 2 diabetes with history of ketoacidosis or diabetic ulcers, or presence of retinopathy, neuropathy, or nephropathy;
* Renal insufficiency defined as a serum creatinine greater than or equal to 1.5 mg/dL (133 µmol/L) at screening;
* Malignant disease within 5 years of screening;
* Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>2 x ULN;
* Thyroid-stimulating hormone (TSH) outside of the normal range;
* Plans on having any surgery (elective or otherwise) during the course of the study;
* Has uncontrolled hypertension (sitting blood pressure \>160/95 mmHg at screening or randomization), uncontrolled hyperlipidemia (triglycerides \[TG\] greater than or equal to 400 mg/dL or low-density lipoprotein cholesterol \[LDL-C\] \>160 mg/dL), or uncontrolled diabetes (HbA1c \>8%);
* History of asthma;
* History of peptic ulcers;
* History of HIV;
* History of undiagnosed allergy, severe allergy, or drug allergy, including history of anaphylaxis, angioedema, bronchospasm, or urticaria;
* Has clinical laboratory test values (chemistry, hematology, or urinalysis) judged to be clinically significant by the investigator;
* Has a physical examination or electrocardiogram (ECG) with significant abnormalities, as judged by the investigator;
* Currently abuses drugs or alcohol or has a history of abuse that in the investigator's opinion could cause the subject to be noncompliant with study procedures;
* Has hypersensitivity to betahistine;
* Has psychiatric or neurological disorders requiring chronic medications (e.g., antidepressants), subjects are to be unlikely to have a major depressive episode (score of lees than or equal to 8) on The Harvard Department of Psychiatry and National Depression Screening Day Scale (THE HANDS) (See Appendix E);
* Chronic or as needed use of antihistamines;
* Has not been on a stable treatment regimen with any of the following medications for a minimum of 90 days prior to screening:
* Hormone replacement therapy;
* Oral contraceptives;
* Antihypertensive agents;
* Metformin;
* Lipid-lowering agents; or
* Thyroid replacement therapy;
* Has been treated over the past 60 days, is currently treated, or is expected to require or undergo treatment with any of the following excluded medications;
* All prescription or over-the-counter agents taken for the purpose of weight reduction, including (but not limited to) the following anti obesity agents:
* Prescription drugs such as orlistat, sibutramine, and phentermine; or
* Over-the-counter antiobesity agents (e.g., herbal supplements or other alternative remedies such as Cortislim, Dexatrim, Acutrim);
* Psychotropic/neurological agents including the following:
* Antipsychotic agents (e.g., olanzapine, clozapine, risperidol, lithium, etc.).
* Antiepileptic agents (e.g., Topamax®, Zonegran®, valproate, carbamazepine); or
* Antidepressant agents including the following: monoamine oxidase inhibitors, bupropion (Wellbutrin®, Zyban®), tricyclic antidepressants, and tetracyclic antidepressants; and selective serotonin reuptake inhibitors (e.g., Prozac®, Paxil®, Zoloft®, etc.);
* Systemic steroids administered by oral, intravenous, or intramuscular route;
* Drugs that directly affect gastrointestinal motility (e.g., Reglan® and Propulsid®, and chronic \[taken for more than 10 days within a 6-month period\] macrolide antibiotics such as erythromycin and newer derivatives);
* Calcitonin (e.g., Miacalcin®);
* Insulin;
* Exenatide (Byetta);
* Sulfonylureas (e.g., Diamicron, Amaryl, Glucotrol, Micronase); or Meglitinides (e.g., Starlix, Prandin)
* Has received any investigational drug within 90 days of screening;
* Receipt of any investigational treatment (drug or device) within 90 days prior to screening;
* Is an immediate family member of personnel directly affiliated with the study at the investigative site, or is personally directly affiliated with the study at the investigative site; or
* Is employed by OBEcure Ltd.

Primary outcomes:
measure: To examine the effect of betahistine on body weight in obese subjects
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Cahaba Research, Inc.
state: Alabama
city: San Diego
country: United States
facility: Scripps Clinic, Nutrition Metabolic Research
state: California
city: Walnut Creek
country: United States
facility: Diablo Clinical Research, Inc.
state: California
city: Miami
country: United States
facility: Miami Research Associates, Inc., Nutrition Division
state: Florida
city: Augusta
country: United States
facility: CSRA Partners in Health, Inc.
state: Georgia
city: Chicago
country: United States
facility: Radiant Research, Inc.
state: Illinois
city: Chicago
country: United States
facility: NCCR
state: Illinois
city: Indianapolis
country: United States
facility: American Health Network
state: Indiana
city: Indianapolis
country: United States
facility: Midwest Institute for Clinical Research
state: Indiana
city: Overland Park
country: United States
facility: Radiant Research, Inc.
state: Kansas
city: Louisville
country: United States
facility: L-MARC Research Center
state: Kentucky
city: Baton Rouge
country: United States
facility: Pennington Biomedical Research Center
state: Louisiana
city: Edina
country: United States
facility: Radiant Research, Inc.
state: Minnesota
city: Chesterfield
country: United States
facility: Diabetes & Endocrinology Specialists
state: Missouri
city: New York
country: United States
facility: Comprehensive Weight Control Program
state: New York
city: Rochester
country: United States
facility: Rochester Clinical Research, Inc.
state: New York
city: Cincinnati
country: United States
facility: Lindner Clinical Trial Center
state: Ohio
city: Portland
country: United States
facility: Covance CRU, Inc.
state: Oregon
city: San Antonio
country: United States
facility: Diabetes & Glandular Disease Research Associates, Inc.
state: Texas
Study officials:
affiliation: Covance CRU, Inc
name: Andrew Ahmann, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Comprehensive Weight Control Program
name: Louis Aronne, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: L-Marc Research Center
name: Harold Bays, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Diabetes & Endocrinology Specialists
name: Norman Fishman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Scripps Clinic, Nutrition Metabolic Research
name: Ken Fujioka, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Radiant Research, Inc
name: Jeffrey Geohas, MD
role: STUDY_DIRECTOR
affiliation: Pennington Biodmedical Research Center
name: Frank Greenway, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Lindner Clinical Trial Center
name: Dean Kereiakes, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Miami Research Associates, Nutrition Division
name: Diane Krieger, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: NCCR
name: Robert Kushner, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: American Health Network
name: Thomas Moretto, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Radiant Research
name: Monica Pierson, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Diabetes & Glandular Disease Research Associates
name: Sherwyn Schwartz, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: CSRA Partners in Health
name: Diane Smith, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Midwest Institute for Clinical Research
name: Philip Toth, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Rochester Clinical Research
name: Mervyn Weerasinghe, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Diablo Clinical Research
name: Richard Weinstein, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Cahaba Research, Inc
name: Lisa Wright, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Radiant Research, Inc.
name: James Zavoral, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: OBEcure Ltd.
name: Nir Barak, MD
role: STUDY_DIRECTOR
affiliation: OBEcure Ltd.
name: Yaffa Beck, PhD
role: STUDY_CHAIR
affiliation: OBEcure Ltd.
name: Ami Eyal, MD
role: STUDY_CHAIR
References: