Clinical trial NCT01834404: Peripheral Pharmacodynamics of Phentermine-Topiramate in Obese Patients
Official title: Peripheral Pharmacodynamics of Phentermine-Topiramate in Obese Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Obesity
Keywords: Obesity
BMI
Incretin
Satiety
Phentermine
Topiramate
Lead sponsor: Mayo Clinic
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2013-04-17
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Our overall goal is to determine the effect of Phentermine and Topiramate ER on gastric emptying, gastric accommodation, satiety, and satiation in obese participants.

Detailed description: Investigators propose a randomized controlled trial of combination phentermine topiramate ER versus placebo given orally for 10-15 days.

At visit 1 subjects had a brief interview, body measurements, and completed 4 questionnaires to rule out any gastrointestinal or significant psychological distress.

At visit 2 subjects did a satiation/nutrient drink test. They drank a nutrient drink until they reached the maximum volume that could be tolerated, symptoms were recorded and blood samples taken at 4 times. They were randomized to one of the arms, and received a 5 day supply of study medication or placebo. The dosing of the study drug was phentermine 3.75 mg / topiramate 23 mg days 1-5.

At visit 3 subjects returned to pick up a nine day supply of study medication or placebo. The dosing of the study drug was increased to phentermine 7.5 mg / topiramate 46 mg days 6-14.

At visit 4 subjects underwent imaging to measure the volume of their stomach with an external camera that revolved around abdomen while they were lying on a table. Stomach volume was checked during fasting, starting 10 min after an intravenous injection of a radioactive material. The subjects ingested more of the liquid nutrient drink and 2 more images were obtained over 30 minutes. On the same day, subjects participated in an all you can eat meal, starting 4 hours after the ingestion of the liquid nutrient drink.

At visit 5 subjects repeated the satiation/nutrient drink test. They drank a nutrient drink until they reached the maximum volume that could be tolerated, symptoms were recorded and blood samples taken at 4 times.

At visit 6 subjects took part in a gastric emptying by scintigraphy test. Subjects were given a scrambled egg breakfast with toast and a glass of milk. The eggs and milk contained a small amount of radioactive substance. At the completion of the meal, subjects stood in front of a special camera and pictures were taken at specific intervals.

Eligibility criteria: INCLUSION CRITERIA:

* Obese subjects with BMI\> 30 Kg/m\^2. Otherwise healthy individuals who are not currently on treatment for cardiac, pulmonary, gastrointestinal, hepatic, renal, hematological, neurological, endocrine (other than hyperglycemia not requiring medical therapy) and unstable psychiatric disease.
* Women of childbearing potential will have negative pregnancy test before initiation of medication.

EXCLUSION CRITERIA:

* Weight \>300 lbs, which is the limit of safety for the SPECT scanner
* Concomitant use of appetite suppressants (i.e., caffeine based or diethylpropion) or orlistat (Xenical®)
* Uncontrolled hypertension (Blood pressure greater than 160/90 mmHg)
* Concentration of fasting glucose greater than 240 mg/dl
* Concentration of triglycerides greater than 400 mg/dl
* Type 1 Diabetes
* Use of anti-diabetic drugs other than metformin,
* History of nephrolithiasis,
* Recurrent major depression, presence or history of suicidal behavior or ideation with intent to act, and current substantial depressive symptoms (Patient Health Questionnaire-9, 21 total score ≥10).
* Concomitant use of Monoamine Oxidase Inhibitors (MAOI) (i.e., phenelzine, selegiline), serotonergic agents, and other centrally acting appetite suppressants
* Significant psychiatric dysfunction based upon screening with the Hospital Anxiety and Depression Scale \[HADS\] self-administered alcoholism screening test (SAAST, substance abuse) and the questionnaire on eating and weight patterns (binge eating disorders and bulimia). If such a dysfunction is identified by a Hospital Anxiety and Depression Scale (HADS) score ≥11 in any of the subscales or difficulties with substance or eating disorders, the participant will be excluded and given a referral letter to his/her primary care doctor for further appraisal and follow-up.
* End stage renal disease or liver cirrhosis
* Intake of medication that could interfere with the interpretation of the study or cause drug interaction (i.e., ketoconazole, erythromycin). Specifically, birth control pill, estrogen replacement therapy, and thyroxine replacement are permissible.

Primary outcomes:
measure: Gastric Emptying of Solids Half-Time (T 1/2)
timeFrame: Day 15, approximately 2 hours after radiolabeled meal was ingested
measure: Fasting Gastric Volume
timeFrame: Day 13, approximately 10 minutes after Technetium (99mTC) injection
measure: Postprandial Gastric Volume
timeFrame: Day 13, approximately 30 minutes after liquid meal
measure: Volume to Fullness
timeFrame: Day 14, approximately 30 minutes after liquid meal
measure: Maximum Tolerated Volume
timeFrame: Day 14, approximately 30 minutes after liquid meal
measure: Buffet Meal Intake
timeFrame: Day 13, approximately 4.5 hours after liquid meal
Secondary outcomes:
measure: Solid Gastric Emptying: Proportion of Meal Emptied at 2 Hours
timeFrame: Day 15, approximately 2 hours after radiolabeled meal was ingested
measure: Solid Gastric Emptying: Proportion Remaining at 4 Hours
timeFrame: Day 15, approximately 4 hours after radiolabeled meal was ingested
measure: Change in Postprandial Gastric Volume
timeFrame: Day 13, approximately approximately 30 min after liquid meal
measure: Fasting Ghrelin
timeFrame: Day 14, before liquid meal
measure: Peak Postprandial Level of Cholecystokinin (CCK)
timeFrame: Day 14, approximately 45 minutes after liquid meal
measure: Peak Postprandial Level of Total Glucagon-Like Peptide-1 (GLP-1)
timeFrame: Day 14, approximately 45 minutes after liquid meal
measure: Peak Postprandial Level of Total Peptide Tyrosine-Tyrosine (PYY)
timeFrame: Day 14, approximately 45 minutes after liquid meal
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic in Rochester
state: Minnesota
Study officials:
affiliation: Mayo Clinic
name: Michael Camilleri, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Acosta A, Camilleri M, Shin A, Vazquez-Roque MI, Iturrino J, Burton D, O'Neill J, Eckert D, Zinsmeister AR. Quantitative gastrointestinal and psychological traits associated with obesity and response to weight-loss therapy. Gastroenterology. 2015 Mar;148(3):537-546.e4. doi: 10.1053/j.gastro.2014.11.020. Epub 2014 Dec 6.