Bulimia
Conditions
Keywords
Eating, Food Intake, Appetite
Brief summary
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
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.
Interventions
DRUGGSKI181771X (CCK-1R agonist)
Drug one trial vs placebo
BEHAVIORALInstructions to binge eat
Subjects will be instructed to binge eat and will also be given either drug or placebo
BEHAVIORALInstructions to eat normally
Subjects will be instructed to eat normally and will also be given either drug or placebo
DRUGPlacebo
Drug one trial vs placebo
Sponsors
GlaxoSmithKline
St. Luke's-Roosevelt Hospital Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Food Intake for 4 mg Dose of CCK Agonist vs Placebo Meal Conditions | 25-30 min after taking drug | Food Intake at 25-30 min after having drug or placebo under normal and binge eating instructions |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fullness Rating | 25-30 min after taking drug | 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). |
| Sickness Report | 25-30 min after drug or placebo | 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) |
Countries
United States
Participant flow
Recruitment details
Recruitment at St. Luke's Hospital from 2/22/08 through 2/19/09
Pre-assignment details
Subject had to rate test food greater than 6 on a 9 point scale of liking and have BMI between 19 and 27
Participants by arm
| Arm | Count |
|---|---|
| 1 MG CCK AGONIST NORMAL EATING Healthy/normal control participants were given both the 1 mg oral cholecystokinin (CCK) agonist (GSKI181771X) and placebo interventions at separate times in a 2 way crossover study design. After ingesting the CCK agonist or placebo, they were instructed to eat until they felt normally full. | 4 |
| 2 MG CCK AGONIST NORMAL EATING Healthy/normal control participants were given both the 2 mg oral cholecystokinin (CCK) agonist (GSKI181771X) and placebo interventions at separate times in a 2 way crossover study design. After ingesting the CCK agonist or placebo, they were instructed to eat until they felt normally full. | 4 |
| 4 MG CCK AGONIST NORMAL EATING Healthy/normal control participants were given both the 4mg oral cholecystokinin (CCK) agonist (GSKI181771X) and placebo interventions at separate times in a 2 way crossover study design. After ingesting the CCK agonist or placebo, they were instructed to eat until they felt normally full. | 8 |
| 4 MG CCK AGONIST BINGE EATING Healthy/normal control participants were given both the 4 mg oral cholecystokinin (CCK) agonist (GSKI181771X) and placebo interventions at separate times in a 2 way crossover study design. After ingesting the CCK agonist or placebo, they were instructed to binge eat as much as they could. | 7 |
| Total | 23 |
Baseline characteristics
| Characteristic | 1 MG CCK AGONIST NORMAL EATING | 2 MG CCK AGONIST NORMAL EATING | 4 MG CCK AGONIST NORMAL EATING | 4 MG CCK AGONIST BINGE EATING | Total |
|---|---|---|---|---|---|
| Age, Continuous | 26 years STANDARD_DEVIATION 10.96 | 26.25 years STANDARD_DEVIATION 3 | 23.75 years STANDARD_DEVIATION 10.77 | 24.00 years STANDARD_DEVIATION 11.64 | 24.65 years STANDARD_DEVIATION 3.94 |
| Region of Enrollment United States | 4 participants | 4 participants | 8 participants | 7 participants | 23 participants |
| Sex: Female, Male Female | 4 Participants | 4 Participants | 8 Participants | 7 Participants | 23 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 23 |
| serious Total, serious adverse events | 0 / 23 |
Outcome results
Primary
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
Time frame: 25-30 min after taking drug
Population: Subjects had to complete all trials of the protocol successfully
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Binge_4mg Drug | Food Intake for 4 mg Dose of CCK Agonist vs Placebo Meal Conditions | 385.69 grams | Standard Error 29.35 |
| Normal_1mg Drug | Food Intake for 4 mg Dose of CCK Agonist vs Placebo Meal Conditions | 447.7 grams | Standard Error 38.64 |
| Normal_2mg Drug | Food Intake for 4 mg Dose of CCK Agonist vs Placebo Meal Conditions | 489.63 grams | Standard Error 45.54 |
| Normal_4mg Drug | Food Intake for 4 mg Dose of CCK Agonist vs Placebo Meal Conditions | 293.79 grams | Standard Error 65.58 |
| Binge - 4mg Placebo | Food Intake for 4 mg Dose of CCK Agonist vs Placebo Meal Conditions | 532.87 grams | Standard Error 53.4 |
| Normal 1 mg Dose Placebo | Food Intake for 4 mg Dose of CCK Agonist vs Placebo Meal Conditions | 468.73 grams | Standard Error 74 |
| Normal_2 mg Dose Placebo | Food Intake for 4 mg Dose of CCK Agonist vs Placebo Meal Conditions | 442.43 grams | Standard Error 61.79 |
| Normal_4 mg Dose Placebo | Food Intake for 4 mg Dose of CCK Agonist vs Placebo Meal Conditions | 421.98 grams | Standard Error 69.26 |
Comparison: Repeated measures ANOVAp-value: 0.007t-test, 2 sided
Secondary
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).
Time frame: 25-30 min after taking drug
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Binge_4mg Drug | Fullness Rating | 144.14 mm | Standard Error 1.82 |
| Normal_1mg Drug | Fullness Rating | 101 mm | Standard Error 9.74 |
| Normal_2mg Drug | Fullness Rating | 128.75 mm | Standard Error 9.84 |
| Normal_4mg Drug | Fullness Rating | 103.13 mm | Standard Error 17.22 |
| Binge - 4mg Placebo | Fullness Rating | 117.57 mm | Standard Error 14.64 |
| Normal 1 mg Dose Placebo | Fullness Rating | 79.75 mm | Standard Error 24.29 |
| Normal_2 mg Dose Placebo | Fullness Rating | 131.25 mm | Standard Error 9.15 |
| Normal_4 mg Dose Placebo | Fullness Rating | 126 mm | Standard Error 5.2 |
Comparison: Each group was compared separately in an overall ANOVA with all dose groups included. The results are presented for the groups which received 4 mg dose and instructions to eat normally (normal group) or to binge eat (binge group). The test is the interaction between drug and group i.e. drug effect difference (placebo minus drug) in fullness between the group instructed to binge and the group instructed to eat normally.p-value: 0.033t-test, 2 sided
Secondary
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)
Time frame: 25-30 min after drug or placebo
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Binge_4mg Drug | Sickness Report | 94.57 mm | Standard Error 22.48 |
| Normal_1mg Drug | Sickness Report | 21 mm | Standard Error 14.58 |
| Normal_2mg Drug | Sickness Report | 10 mm | Standard Error 7.07 |
| Normal_4mg Drug | Sickness Report | 17.5 mm | Standard Error 9.64 |
| Binge - 4mg Placebo | Sickness Report | 61.14 mm | Standard Error 20.79 |
| Normal 1 mg Dose Placebo | Sickness Report | 3 mm | Standard Error 1.35 |
| Normal_2 mg Dose Placebo | Sickness Report | 10 mm | Standard Error 8.72 |
| Normal_4 mg Dose Placebo | Sickness Report | 17.25 mm | Standard Error 8.43 |
Comparison: Tests the difference between drug and placebo for group = binge instructionsp-value: <0.014ANOVA