Effects of RM-493 on Energy Expenditure in Obese Individuals
- RM-493 is a drug that stimulates parts of the brain that control eating and metabolism. It has helped to reduce body weight and improve insulin sensitivity in lab tests. However, it is not fully known whether RM-493 causes weight loss by just decreasing appetite or by increasing metabolism or both. Researchers want to see how RM-493 affects metabolism and hormones that affect the metabolic rate. They also want to see how RM-493 affects appetite by assessing feelings of hunger and fullness. They will study this drug in people who are obese but are otherwise in good health.
- To see how RM-493 affects metabolic rate and appetite in obese but otherwise healthy individuals.
- Individuals between 18 and 50 years old who are obese (body mass index between 30 and 40 kg/m2) but are otherwise healthy.
- The study consists of three phases. The first phase is the screening visit. The second phase is an 8-day inpatient stay. The final phase is a follow-up phone call one week after the end of the second phase.
- Participants will be divided into two groups. One group will receive the study drug first, followed by a placebo. The other group will receive the placebo followed by the study drug. The study drug and placebo will be given under the skin for 3 days each by a small device (OmniPod) that normally is used to give insulin to people with diabetes.
- Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. They will also meet with a dietitian. The OmniPod device will be demonstrated before use.
- Participants will have the following procedures during their 8-day inpatient stay:
- Daily exercise routine (walking on treadmill) after setting a comfortable pace (miles per hour) during an exercise test
- Wear physical activity monitors
- Body composition study to measure amounts of fat and muscle
- Calorie controlled study diet
- Study drug/placebo dose through the OmniPod (Days 2 through 4 and 5 through 7)
- Metabolic rate studies using a cart or the metabolic chamber
- Daily blood samples
- Urine collection for 24 hours
- Questions about weight history and appetite
- About a week after the inpatient stay, participants will have a followup phone call to ask about any side effects from the study.
|Study Design:||Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Primary Purpose: Treatment
|Official Title:||A Phase 1b, Randomized, Double-Blind, Placebo-Controlled, Multiple Dose, 2-Period Crossover Study to Evaluate the Effect of RM-493 on Energy Expenditure in Obese Subjects|
- Resting energy expenditure measured in a room calorimeter during continuous subcutaneous infusion of RM-493 or placebo in obese healthy subjects [ Time Frame: day 4 and day 7 ] [ Designated as safety issue: No ]
- Total energy expenditure measured in a room calorimeter during continuous subcutaneous infusion of RM-493 or placebo in obese healthy subjects [ Time Frame: day 4 and day 7 ] [ Designated as safety issue: No ]
|Study Start Date:||May 2013|
|Estimated Study Completion Date:||December 2014|
|Estimated Primary Completion Date:||December 2014 (Final data collection date for primary outcome measure)|
Active Comparator: RM-493
Double blind RM-493 will be administered at a dose of 1 mg/24 hrs via subcutaneous infusion for 3 days
Sterile solution (2mg/ml) for subcutaneous infusion
Placebo Comparator: Placebo
Double blind placebo will be administered via subcutaneous infusion for 3 days
Sterile solution (vehicle) for subcutaneous infusion
Obesity is a chronic relapsing health problem and a strong risk factor for type 2 diabetes, hypertension, heart disease and stroke. Life expectancy is shorter in obese individuals who often suffer from costly related co-morbidities such as certain cancers, liver disease, osteoarthritis, sleep apnea and depression. Weight loss improves the co-morbidities. Diet and exercise are effective in the short term, but are rarely effective over a span of years. New therapies are needed especially for patients with obesity. The melanocortin system, and specifically, melanocortin 4 receptor (MC4R) is involved in the regulation of energy homeostasis and body weight. This role is validated in human genetic mutations, and in animal models of obesity, stimulation of MC4R reduces food intake and increases metabolic rate, causing a reduction in body weight.
RM-493 is a potent, selective peptide agonist for the MC4R that suppressed food intake and reduced body weight in preclinical studies. RM-493 has been studied in single dose and multiple ascending dose clinical studies in obese volunteers. This study is a randomized, double-blind, placebo-controlled, multiple-dose, 2-period, crossover study to assess the effects of RM-493 on resting energy expenditure measured in a room calorimeter. Twelve obese but otherwise healthy adult subjects between the ages of 18 and 50 inclusive, will be enrolled and randomized to one of 2 treatment sequences (RM-493 then placebo; or placebo then RM-493) over an 8-day study interval. Components of 24-hour energy expenditure, exercise induced energy expenditure, spontaneous physical activity, respiratory quotient, safety and pharmacokinetic data will be collected.
|Contact: Pamela M Staker, C.R.N.P.||(301) 451-8893||PAMELA.STAKER2@NIH.GOV|
|Contact: Monica C Skarulis, M.D.||(301) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL) 800-411-1222 ext TTY8664111010 email@example.com|
|Principal Investigator:||Monica C Skarulis, M.D.||National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)|