Effect of a CCK-1R Agonist on Food Intake in Humans

Study Overview
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Brief Summary
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The ultimate aim of this study is to test the hypothesis that the oral cholecystokinin (CCK) agonist GSKI181771X will reduce the size of a binge meal among individuals with Bulimia Nervosa. The study will be conducted in phases. First, an effective dose for reducing food intake, when normal subjects eat normally will be attained. Next, it will be determined whether intake at this dose is reduced in control subjects instructed to eat to capacity. If the dose is still effective compared to placebo, the same dose will be tested in patients with bulimia nervosa.

Detailed Description
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This study tests the hypothesis that an oral CCK antagonist GSKI181771X will reduce the size of a binge meal. It was intended to study the effects of increasing doses on antagonist on normal individuals to find an effective dose in a non-binge meal before moving to a binge meal. Once the effects of the antagonist on a binge meal were found, the compound would be used on patients with bulimia nervosa. However, the product expired and more was not available before the patients were tested. Data are presented for the normal participants who were instructed to eat normally, followed by a group that was instructed to binge eat. Comparisons were made between groups with different instructions and between binge and normal meals.

Official Title
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Effect of a CCK-1R Agonist on Food Intake in Humans

Conditions
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Bulimia

Intervention / Treatment
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* Drug: GSKI181771X (CCK-1R agonist)
* Behavioral: Instructions to binge eat
* Behavioral: Instructions to eat normally
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Both controls and patients will be female, 18 to 45 years old, and within 80-120% of ideal body weight (Metropolitan Life Insurance, 1983). Inclusion and exclusion will be evaluated using the following guidelines: Normal Controls: No current or past psychiatric illness No history of binge eating or vomiting 80-120% ideal weight Of non-childbearing potential (i.e. physiologically incapable of becoming pregnant or surgically sterile) If of childbearing potential, willing to use an acceptable method of birth-control (please see list in Exclusion section) Patients with Bulimia Nervosa: DSM-IV (diagnostic statistical manual - American Psychiatric Association) criteria for bulimia nervosa Duration of illness > 1 year Purging after binges via self-induced vomiting (Same as controls for remaining inclusion criteria) Exclusion Criteria: Normal Controls: Significant medical illness: CBC, Chem-1, serum electrolytes (sodium, potassium, chloride, CO2), glucose, BUN (blood urea nitrogen), creatinine, Alk Phos, ALT (SGPT), AST (SGOT), LDH, total bilirubin, total protein, albumin, globulin, A/G ratio, calcium, phosphorus, uric acid, cholesterol, triglyceride ALT outside of upper limit of normal: Chem-1 History of gallstones, pancreatitis or cholecystitis Current medication Hypersensitivity to benzodiazepines (contraindication in DCSI v02, 1-March-2006) Drug or alcohol abuse in last 3 mts Pregnancy Unable or unwilling to use highly effective methods of contraception for the duration of the study until an insignificant amount of the investigational product remains in the subject (i.e. at least 5 terminal phase half-lives). Examples of highly effective methods of contraception are: Implants of levonorgestrel, or Injectable progestogen, or Oral birth control pills for at least 3 monthly cycles prior to administration of study drug + continuation for 24 hrs after last dose of study drug, or Double-barrier method (e.g. condom, diaphragm) with spermicide Note-Significant medical illness is any illness requiring continued care, i.e. chronic medication. Examples include hypertension, diabetes, and systemic lupus erythematosis. Subjects with seasonal allergies or occasional urinary tract infections will be included. Patients with Bulimia Nervosa: Same as controls

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 1 'Instructions to eat normally'<br>'Instructions to eat normally' Placebo 1 mg dose | Behavioral: Instructions to eat normally<br>* Subjects will be instructed to eat normally and will also be given either drug or placebo<br>Drug: Placebo<br>* Drug one trial vs placebo<br>|
| Active Comparator: 2 'Instructions to eat normally'<br>'Instructions to eat normally' drug 1 mg dose 'GSKI181771X (CCK-1R agonist)' | Drug: GSKI181771X (CCK-1R agonist)<br>* Drug one trial vs placebo<br>* Other names: GSKI181771X;Behavioral: Instructions to eat normally<br>* Subjects will be instructed to eat normally and will also be given either drug or placebo<br>|
| Placebo Comparator: 3 'Instructions to eat normally'<br>'Instructions to eat normally' 2 mg placebo | Behavioral: Instructions to eat normally<br>* Subjects will be instructed to eat normally and will also be given either drug or placebo<br>Drug: Placebo<br>* Drug one trial vs placebo<br>|
| Active Comparator: 4 'Instructions to eat normally'<br>'Instructions to eat normally' 2 mg drug 'GSKI181771X (CCK-1R agonist)' | Drug: GSKI181771X (CCK-1R agonist)<br>* Drug one trial vs placebo<br>* Other names: GSKI181771X;Behavioral: Instructions to eat normally<br>* Subjects will be instructed to eat normally and will also be given either drug or placebo<br>|
| Placebo Comparator: 5 'Instructions to eat normally'<br>'Instructions to eat normally' 4 mg placebo | Behavioral: Instructions to eat normally<br>* Subjects will be instructed to eat normally and will also be given either drug or placebo<br>Drug: Placebo<br>* Drug one trial vs placebo<br>|
| Active Comparator: 6 'Instructions to eat normally'<br>'Instructions to eat normally' 4 mg drug 'GSKI181771X (CCK-1R agonist)' | Drug: GSKI181771X (CCK-1R agonist)<br>* Drug one trial vs placebo<br>* Other names: GSKI181771X;Behavioral: Instructions to eat normally<br>* Subjects will be instructed to eat normally and will also be given either drug or placebo<br>|
| Placebo Comparator: 7 Instructions to binge eat<br>Instructions to binge eat 4 mg placebo | Behavioral: Instructions to binge eat<br>* Subjects will be instructed to binge eat and will also be given either drug or placebo<br>Drug: Placebo<br>* Drug one trial vs placebo<br>|
| Active Comparator: 8 Instructions to binge eat<br>Instructions to binge eat 4 mg drug 'GSKI181771X (CCK-1R agonist)' | Drug: GSKI181771X (CCK-1R agonist)<br>* Drug one trial vs placebo<br>* Other names: GSKI181771X;Behavioral: Instructions to binge eat<br>* Subjects will be instructed to binge eat and will also be given either drug or placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Food Intake for 4 mg Dose of CCK Agonist vs Placebo Meal Conditions | Food Intake at 25-30 min after having drug or placebo under normal and binge eating instructions | 25-30 min after taking drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fullness Rating | rating of How full do you feel by marking the feeling on a 150 mm line anchored at one end from 0 (not at all) to 150 (most imaginable). | 25-30 min after taking drug | 
| Sickness Report | Response to question How sick do you feel measured on a 150 mm line anchored by none at all (0 mm left end) and extremely (150 mm right end) | 25-30 min after drug or placebo | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Eating, Food Intake, Appetite