Regulation of FGF21 by Nutritional Challenges

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by Beth Israel Deaconess Medical Center
Sponsor:
Information provided by (Responsible Party):
Jody Dushay, Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier:
NCT00968747
First received: July 31, 2009
Last updated: November 13, 2013
Last verified: November 2013
  Purpose

The purpose of this study is to examine how acute nutritional challenges affect levels of several proteins involved in metabolism. These proteins will be measured in blood and fat tissue.

This study will have several aims.

One aim is to examine the effect of 72 hours of fasting on fibroblast growth factor-21 (FGF-21) levels. Participants will spend 3 days and nights in the Clinical Research Center at the Beth Israel Deaconess Medical Center in Boston, MA. Daily blood samples will be taken. Two fat samples will be taken prior to and at the end of the fast. A subset of participants will also have two MRIs, one prior to and one at the end of the fast. We will study healthy adults and obese adults with liver-biopsy-diagnosed non-alcoholic fatty liver disease (NAFLD).

Another aim is to examine the effect of low-calorie diet on FGF-21 levels. Subjects will follow a hypocaloric diet that will be designed to achieve 3-5% weight loss. We will enroll participants with liver-biopsy-diagnosed non-alcoholic fatty liver disease. Participants will report weekly to the Clinical Research Center at Beth Israel Deaconess Medical Center for weight measurements. Blood will be drawn before and after the weight loss. Participants will also have an MRI before and after the weight loss.

Another aim of the study is to examine the effect of acute ingestion of glucose and fructose on serum FGF21 levels. Subjects in this study will be lean volunteers and individuals with metabolic syndrome.


Condition Intervention
Metabolism
Fasting
Non-alcoholic Fatty Liver Disease (NAFLD)
Behavioral: Fasting
Behavioral: Diet
Dietary Supplement: oral carbohydrate challenge

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: The Effect of Acute Nutritional Challenges on FGF21 Levels in Humans

Resource links provided by NLM:


Further study details as provided by Beth Israel Deaconess Medical Center:

Primary Outcome Measures:
  • Fibroblast Growth Factor 21 levels in serum and fat [ Time Frame: before and after dietary intervention ] [ Designated as safety issue: No ]
    Change in FGF21 levels following nutritional intervention.


Secondary Outcome Measures:
  • Polymerase 1 and Transcript Release Factor levels in fat [ Time Frame: Prior to fasting and at the end of the 72-hour fast in healthy participants and participants with NAFLD ] [ Designated as safety issue: No ]
  • Urine and serum ketosis [ Time Frame: Daily during the 72-hour fast for healthy participants and participants with NAFLD ] [ Designated as safety issue: No ]
  • Hepatic fat content [ Time Frame: Before and after the 72-hour fast or hypocaloric diet in participants with NAFLD ] [ Designated as safety issue: No ]
  • change in serum triglyceride levels [ Time Frame: following fructose and glucose ingestion ] [ Designated as safety issue: No ]
  • change in glucose and insulin levels [ Time Frame: following fructose and glucose ingestion ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: July 2009
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Fasting (Healthy). No longer recruiting.

Participants will fast for 72 hours during an inpatient stay at the Beth Israel Deaconess Medical Center in Boston, MA. During the fast, participants will receive only water and vitamins. Blood samples will be collected daily and two fat samples will be obtained by a trained surgeon.

(We are no longer recruiting for Study Arm A).

Behavioral: Fasting
Participants will fast for 72 hours and may consume only water and vitamins.
Experimental: Fasting (NAFLD)
Participants with liver-biopsy diagnosed non-alcoholic fatty liver disease (NAFLD) will fast for 72 hours during an inpatient stay at the Beth Israel Deaconess Medical Center in Boston, MA. Blood samples will be collected daily, and participants will have an MRI before and after the fast.
Behavioral: Fasting
Participants will fast for 72 hours and may consume only water and vitamins.
Experimental: Hypocaloric diet (NAFLD)
Participants will follow a low-calorie diet until they lose 3-5% of their body weight. Participants will have weekly outpatient visits at Beth Israel Deaconess Medical Center in Boston, MA for weight measurements. Participants will have blood drawn before and after the diet. Participants will also have an MRI before and after the diet.
Behavioral: Diet
Participants will follow a low-calorie diet until they lose 3-5% of their body weight.
Experimental: FGF21 response to oral carbohydrate challenges
subjects will ingest drinks containing fructose, glucose or a mixture of fructose and glucose. blood will be drawn postprandially at specified timepoints for 4 hours
Behavioral: Diet
Participants will follow a low-calorie diet until they lose 3-5% of their body weight.
Dietary Supplement: oral carbohydrate challenge

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

72-hour fast in healthy volunteers (Study Arm A):

Inclusion Criteria:

  • Age 18-50 years
  • Body Mass Index 21-26 kg/m^2
  • Ability to give informed consent
  • Ability to follow verbal and written instructions in English

Exclusion Criteria:

  • Type 1 or Type 2 diabetes mellitus diagnosed according to the American Diabetes Association criteria
  • Coronary heart disease (history of myocardial infarction, unstable angina pectoris, or congestive heart failure)
  • Tobacco, marijuana, or intravenous drug use within 1 year of screening visit
  • Recent weight change (>3 kg within 6 months of screening visit)
  • Malignancy treated with chemotherapy within past 3 years
  • History of depression, psychosis, or other psychiatric illness requiring hospitalization
  • History of hyperthyroidism
  • Renal insufficiency (creatinine clearance < 50 ml/min)
  • Transaminases > 2X above the normal range
  • Known liver disease
  • Pregnancy within 12 months of screening visit
  • Lactation within 12 months of screening visit
  • Failure to use medically approved contraceptive methods (oral contraceptive, 2 barrier methods, surgical sterilization)
  • History of an eating disorder (anorexia, bulimia, or laxative abuse)
  • History of surgery for the treatment of obesity (gastric banding, gastric bypass, gastric stapling)
  • New diagnosis of hypothyroidism within 1 year of screening visit or change in dose of thyroid hormone within 3 months of screening visit
  • History of alcohol abuse within the past 3 years
  • History of keloid formation
  • History of allergy to lidocaine or marcaine
  • Use of plavix, coumadin, or heparin

    72-hour fast or hypocaloric diet in subjects with non-alcoholic fatty liver disease (NAFLD) (Study Arms B & C):

Inclusion Criteria:

  • Age 18-60
  • BMI 25-45 kg/m^2
  • Known nonalcoholic fatty liver disease based on liver biopsy
  • Ability to give informed consent
  • Ability to follow verbal and written instructions in English

Exclusion Criteria:

  • Type I diabetes mellitus diagnosed according to the American Diabetes Association criteria or Type II diabetes mellitus with A1c > 7.5% or taking metformin or thiazolidinediones
  • Coronary Heart Disease (history of myocardial infarction, unstable angina pectoris, or congestive heart failure)
  • Uncontrolled hypertension (BP > 150/90 mmHg on or off antihypertensive medication)
  • Tobacco, marijuana, or intravenous drug use within 1 year of screening visit
  • Recent weight change (> 3 kg within 6 months of screening visit)
  • Malignancy treated with chemotherapy within the past 3 years
  • History of depression, psychosis, or other psychiatric illness requiring hospitalization
  • History of hypo or hyperthyroidism
  • Renal insufficiency (creatinine clearance < 50 ml/min)
  • Pregnancy within 12 months of screening visit
  • Lactation within 12 months of screening visit
  • Failure to use medically approved contraceptive methods (oral contraceptive, 2 barrier methods, surgical sterilization)
  • History of an eating disorder (anorexia, bulimia, or laxative abuse)
  • History of surgery for the treatment of obesity (gastric banding, gastric bypass, gastric stapling)
  • New diagnosis of hypo or hyperthyroidism within 1 year of screening visit or change in dose of thyroid hormone within 3 months of screening visit
  • History of alcohol abuse within the past 3 years
  • Cardiac pacemaker or aneurysm clips
  • Metal implants in the body (pins, plates, shrapnel, intact bullets, IUD)
  • Claustrophobia
  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: NCT00968747

Contacts
Contact: Jody Dushay, MD 617-735-3281 jdushay@bidmc.harvard.edu

Locations
United States, Massachusetts
Beth Israel Deaconess Medical Center Recruiting
Boston, Massachusetts, United States, 02215
Sub-Investigator: Eleftheria Maratos-Flier, MD         
Sub-Investigator: Elena Toschi, MD         
Sponsors and Collaborators
Beth Israel Deaconess Medical Center
Investigators
Principal Investigator: Jody Dushay, MD Beth Israel Deaconess Medical Center
  More Information

No publications provided

Responsible Party: Jody Dushay, MD, Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier: NCT00968747     History of Changes
Other Study ID Numbers: 2009P-000073
Study First Received: July 31, 2009
Last Updated: November 13, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Beth Israel Deaconess Medical Center:
Fasting
Fast
Metabolism
healthy
diet
study
manipulation
dietary
FGF21
Fibroblast growth factor
PTRF
Polymerase 1 and transcript release factor
adipose
fat
blood
inpatient
outpatient
NAFLD

Additional relevant MeSH terms:
Fatty Liver
Liver Diseases
Digestive System Diseases

ClinicalTrials.gov processed this record on July 28, 2014