Effects of RM-493 on Energy Expenditure in Obese Individuals
Condition: Obesity; Morbid Obesity
MeSH terms: Obesity; Obesity, Morbid
Study type: Interventional
Phase: Phase 1

Summary: 
      Background:

      - 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.

      Objectives:

      - To see how RM-493 affects metabolic rate and appetite in obese but otherwise healthy
      individuals.

      Eligibility:

      - Individuals between 18 and 50 years old who are obese (body mass index between 30 and 40
      kg/m2) but are otherwise healthy.

      Design:

        -  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.
    

Detailed description: 
      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.
    

Intervention name(s): Placebo; RM-493
Intervention type(s): Drug; Drug
Intervention description(s): Sterile solution (vehicle) for subcutaneous infusion; Sterile solution (2mg/ml) for subcutaneous infusion
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: 24 Hour Energy Expenditure; Resting Energy Expenditure; Obesity; Healthy Volunteers