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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00640757
Recruitment Status : Completed
First Posted : March 21, 2008
Last Update Posted : December 18, 2015
Orentreich Foundation for the Advancement of Science, Inc.
Information provided by (Responsible Party):
Frank Greenway, Pennington Biomedical Research Center

Brief 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.

Condition or disease Intervention/treatment Phase
Metabolic Syndrome Dietary Supplement: Methionine deficient diet Dietary Supplement: Methionine sufficient diet Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 56 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Methionine-Restriction Diet (MRD) in Obese Adults With Metabolic Syndrome
Study Start Date : July 2006
Actual Primary Completion Date : December 2008
Actual Study Completion Date : December 2008

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. Weight loss [ Time Frame: Every 2 weeks ]

Secondary Outcome Measures :
  1. Improve glucose metabolism [ Time Frame: Baseline and end of study ]

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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Ages Eligible for Study:   21 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00640757

Sponsors and Collaborators
Pennington Biomedical Research Center
Orentreich Foundation for the Advancement of Science, Inc.
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Principal Investigator: Thomas W Gettys, Ph.D. Pennington Biomedical Research Center
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Frank Greenway, Professor, Pennington Biomedical Research Center Identifier: NCT00640757    
Other Study ID Numbers: PBRC 26009
First Posted: March 21, 2008    Key Record Dates
Last Update Posted: December 18, 2015
Last Verified: December 2015
Keywords provided by Frank Greenway, Pennington Biomedical Research Center:
Metabolic syndrome
Glucose Metabolism
Amino acid
Insulin clamp
Additional relevant MeSH terms:
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Metabolic Syndrome
Pathologic Processes
Insulin Resistance
Glucose Metabolism Disorders
Metabolic Diseases