Methionine-Restriction Diet (MRD) in Obese Adults With Metabolic Syndrome

This study has been completed.
Sponsor:
Collaborator:
Orentreich Foundation for the Advancement of Science, Inc.
Information provided by:
Pennington Biomedical Research Center
ClinicalTrials.gov Identifier:
NCT00640757
First received: March 18, 2008
Last updated: May 31, 2009
Last verified: May 2009
  Purpose

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.


Condition Intervention Phase
Metabolic Syndrome
Dietary Supplement: Methionine deficient diet
Dietary Supplement: Methionine sufficient diet
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Methionine-Restriction Diet (MRD) in Obese Adults With Metabolic Syndrome

Resource links provided by NLM:


Further study details as provided by Pennington Biomedical Research Center:

Primary Outcome Measures:
  • Weight loss [ Time Frame: Every 2 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Improve glucose metabolism [ Time Frame: Baseline and end of study ] [ Designated as safety issue: No ]

Enrollment: 56
Study Start Date: July 2006
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Low Methionine 1
Methionine deficient diet
Dietary Supplement: Methionine deficient diet
Hominex with a low protein diet
Other Names:
  • Hominex
  • Methionine
Placebo Comparator: Placebo 2
Placebo comparator methionine complete diet
Dietary Supplement: Methionine sufficient diet
Hominex, low protein diet and methionine capsules
Other Names:
  • Hominex
  • Methionine capsules
  • Low protein diet

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.

  Eligibility

Ages Eligible for Study:   21 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Male or female between the ages of 21 to 60, inclusive
  • Waist greater than 40 inches for men and 35 inches for women
  • Weight has been stable for at least 6 months (no more than 5 pounds gained or lost)
  • For women of childbearing potential: subject must be willing to use acceptable form of contraception (pill, condom, diaphragm etc.)
  • At least 2 of the following:

HDL cholesterol

  • Men < 40 mg/dL
  • Women < 50 mg/dL Triglycerides ≥150 mg/dL Blood pressure ≥130/≥ 85 mmHg Fasting glucose ≥110-125 mg/dL

Exclusion Criteria:

  • Type 1 or Type 2 diabetes
  • History of heart attack or stroke
  • Pregnant or breastfeeding or planning to become pregnant during the study
  • Cancer (other than non-melanoma skin) within the last 5 years
  • Significant illness requiring medication
  • Inability to read and follow directions in English
  • Donated blood in the last 2 months.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00640757

Sponsors and Collaborators
Pennington Biomedical Research Center
Orentreich Foundation for the Advancement of Science, Inc.
Investigators
Principal Investigator: Thomas W Gettys, Ph.D. Pennington Biomedical Research Center
  More Information

No publications provided by Pennington Biomedical Research Center

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Thomas Gettys, Ph.D., Pennington Biomedical Research Center
ClinicalTrials.gov Identifier: NCT00640757     History of Changes
Other Study ID Numbers: PBRC26009
Study First Received: March 18, 2008
Last Updated: May 31, 2009
Health Authority: United States: Institutional Review Board

Keywords provided by Pennington Biomedical Research Center:
Methionine
Metabolic syndrome
Glucose Metabolism
Amino acid
Insulin clamp

Additional relevant MeSH terms:
Metabolic Syndrome X
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases

ClinicalTrials.gov processed this record on August 25, 2014