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Regulation of FGF21 by Nutritional Challenges

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ClinicalTrials.gov Identifier: NCT00968747
Recruitment Status : Active, not recruiting
First Posted : August 31, 2009
Last Update Posted : April 10, 2018
Sponsor:
Information provided by (Responsible Party):
Jody Dushay, Beth Israel Deaconess Medical Center

Brief Summary:

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). THIS STUDY ARM IS CURRENTLY NOT RECRUITING

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.

THIS ARM IS CURRENTLY NOT RECRUITING

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

THIS ARM IS CURRENTLY RECRUITING


Condition or disease Intervention/treatment Phase
Fasting Non-alcoholic Fatty Liver Disease (NAFLD) Behavioral: Fasting Behavioral: Diet Dietary Supplement: oral carbohydrate challenge Not Applicable

Detailed Description:
Participation in this study involves fasting overnight, drinking a sweet beverage, and several blood draws through an IV line. Each subject may drink up to 5 different sweet beverages, separated by 2 weeks.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: The Effect of Acute Nutritional Challenges on FGF21 Levels in Humans
Study Start Date : July 2009
Estimated Primary Completion Date : December 31, 2018
Estimated Study Completion Date : April 30, 2019


Arm Intervention/treatment
Experimental: Fasting (Healthy).
Participants 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 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.
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: Oral carbohydrate challenge
Participants will fast for 16 hours overnight then ingest drinks containing fructose, glucose or a mixture of fructose and glucose. Blood will be drawn postprandially at specified timepoints for up to 5 hours
Dietary Supplement: oral carbohydrate challenge
Participants will fast for 16 hours and then drink a beverage containing glucose, fructose or a mixture of both



Primary Outcome Measures :
  1. Fibroblast Growth Factor 21 levels in serum and fat [ Time Frame: before and after dietary intervention ]
    Change in FGF21 levels following nutritional intervention.


Secondary Outcome Measures :
  1. 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 ]
  2. Urine and serum ketosis [ Time Frame: Daily during the 72-hour fast for healthy participants and participants with NAFLD ]
  3. Hepatic fat content [ Time Frame: Before and after the 72-hour fast or hypocaloric diet in participants with NAFLD ]
  4. change in serum triglyceride levels [ Time Frame: following fructose and glucose ingestion ]
  5. change in glucose and insulin levels [ Time Frame: following fructose and glucose ingestion ]


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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
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

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 ClinicalTrials.gov identifier (NCT number): NCT00968747


Locations
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Beth Israel Deaconess Medical Center
Investigators
Principal Investigator: Jody Dushay, MD Beth Israel Deaconess Medical Center

Responsible Party: Jody Dushay, MD, Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier: NCT00968747     History of Changes
Other Study ID Numbers: 2009P-000073
First Posted: August 31, 2009    Key Record Dates
Last Update Posted: April 10, 2018
Last Verified: April 2018

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

Additional relevant MeSH terms:
Liver Diseases
Fatty Liver
Non-alcoholic Fatty Liver Disease
Digestive System Diseases