Methionine-Restriction Diet (MRD) in Obese Adults With Metabolic Syndrome
Condition: Metabolic Syndrome
MeSH terms: Metabolic Syndrome; Syndrome
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this study is to determine if limiting dietary methionine (MET), one of the 10
      essential amino acids (which make up proteins), causes weight loss and/or improves glucose
      metabolism.
    

Detailed description: 
      Methionine deficient diets have been shown to increase metabolic rate, decrease weight and
      extend lifespan in rodents. A methionine deficient diet has been tested for 17 weeks in
      humans without adverse events and with an average weight loss of 8 kg. This study will test
      the ability of a low methionine diet to cause weight loss and improve the metabolic syndrome.
      The metabolic syndrome is driven by insulin resistance which is associated with abdominal
      fat, so this study hopes to reduce visceral fat, body weight and improve insulin resistance.

      Twenty-four healthy males or females 21 to 60 years of age, inclusive with a stable weight
      and a waist circumference >40" in men and >35" in women will participate in this study.
      Subjects will need at least two of the following: 1) HDL cholesterol < 40 mg/dL in men or <
      50 mg/dl in women; 2) triglycerides > 150 mg/dL, 3) blood pressure >130/85 mmHg; 4) fasting
      glucose 110-125 mg/dL. Subjects who have diabetes, a history of heart attack, stroke, have
      had cancer in the last five years or take chronic medication for a significant illness will
      be excluded.

      Subjects will have a medical history, physical examination, chemistry panel, complete blood
      count (CBC), electrocardiogram, DEXA, abdominal CT scan to quantitate visceral fat, and blood
      will be sent to Orentreich for glucose, insulin, C-peptide, lipid profile with particle size,
      free fatty acids, adiponectin, leptin, high-sensitivity C-reactive protein, and insulin-like
      growth factor-1. Subjects will also undergo a hyperinsulinemic, euglycemic clamp to
      quantitate insulin resistance during an 18 hr inpatient stay, and will spend 24 hours in the
      metabolic chamber to measure metabolic rate. Subjects will then be placed on a diet of
      Hominex-2, a drink that will give them their protein in an amount based on their body weight,
      and they will see a dietitian who will give them a list of food they can eat consisting
      mainly of fruits, vegetables and a small amount of grains. Calories will not be restricted
      and subjects will receive a choline supplement of 500 mg/d. Subjects will be randomized to
      receive capsules containing methionine or placebo based on their body weight. The two groups
      will be on 2mg/kg/d or 23 mg/kg/d of methionine.

      Participants will return to PBRC every 2 weeks throughout the 16-week diet period to meet
      with the dietician, have weight and vital signs recorded, and have fasting blood drawn every
      4 weeks to be sent to Orentreich for compliance measures.

      The physical exam, multi-slice CT scan, DEXA, inpatient admission for euglycemic
      hyperinsulinemic clamp, metabolic chamber stay, and the blood testing obtained at screening
      and baseline will be repeated at the completion of the 16 week diet period.

      There are no known risks to the low methionine diet, but some people may have
      gastrointestinal upsets when they change their diet. The risk of the CT scan is exposure to
      x-radiation equivalent to a front and side view chest x-ray. The risk of the DEXA is the
      exposure to x-irradiation equivalent to spending 12 hours in the sunshine. There are no risks
      to staying in the metabolic chamber. The hyperinsulinemic, euglycemic clamp could cause low
      blood sugar. This will be avoided by frequent monitoring of blood sugar, and if the low blood
      sugar were to occur, the test would be stopped and sugar given through the intravenous line.
      The testing of blood involves the discomfort of a needle going into an arm vein, bruising and
      rarely fainting or infection. These risks will be minimized by trained technicians using
      sterile needles.
    

Intervention name(s): Methionine deficient diet; Methionine sufficient diet
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Hominex with a low protein diet; Hominex, low protein diet and methionine capsules
Other intervention name(s): Hominex; Methionine; Hominex; Methionine capsules; Low protein diet
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Methionine; Metabolic syndrome; Glucose Metabolism; Amino acid; Insulin clamp