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Regulation of FGF21 by Nutritional Challenges

Primary Purpose

Fasting, Non-alcoholic Fatty Liver Disease (NAFLD)

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Fasting
Fasting
Diet
oral carbohydrate challenge
Sponsored by
Beth Israel Deaconess Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Fasting focused on measuring 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

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Beth Israel Deaconess Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Fasting (Healthy).

Fasting (NAFLD)

Hypocaloric diet (NAFLD)

Oral carbohydrate challenge

Arm Description

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).

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.

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.

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

Outcomes

Primary Outcome Measures

Fibroblast Growth Factor 21 levels in serum and fat
Change in FGF21 levels following nutritional intervention.

Secondary Outcome Measures

Polymerase 1 and Transcript Release Factor levels in fat
Urine and serum ketosis
Hepatic fat content
change in serum triglyceride levels
change in glucose and insulin levels

Full Information

First Posted
July 31, 2009
Last Updated
August 9, 2023
Sponsor
Beth Israel Deaconess Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT00968747
Brief Title
Regulation of FGF21 by Nutritional Challenges
Official Title
The Effect of Acute Nutritional Challenges on FGF21 Levels in Humans
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Completed
Study Start Date
July 2009 (undefined)
Primary Completion Date
July 31, 2023 (Actual)
Study Completion Date
July 31, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Beth Israel Deaconess Medical Center

4. Oversight

Data Monitoring Committee
No

5. Study Description

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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Fasting, Non-alcoholic Fatty Liver Disease (NAFLD)
Keywords
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

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Fasting (Healthy).
Arm Type
Experimental
Arm Description
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).
Arm Title
Fasting (NAFLD)
Arm Type
Experimental
Arm Description
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.
Arm Title
Hypocaloric diet (NAFLD)
Arm Type
Experimental
Arm Description
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.
Arm Title
Oral carbohydrate challenge
Arm Type
Experimental
Arm Description
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
Intervention Type
Behavioral
Intervention Name(s)
Fasting
Intervention Description
Participants will fast for 72 hours and may consume only water and vitamins.
Intervention Type
Behavioral
Intervention Name(s)
Fasting
Intervention Description
Participants will fast for 72 hours and may consume only water and vitamins.
Intervention Type
Behavioral
Intervention Name(s)
Diet
Intervention Description
Participants will follow a low-calorie diet until they lose 3-5% of their body weight.
Intervention Type
Dietary Supplement
Intervention Name(s)
oral carbohydrate challenge
Intervention Description
Participants will fast for 16 hours and then drink a beverage containing glucose, fructose or a mixture of both
Primary Outcome Measure Information:
Title
Fibroblast Growth Factor 21 levels in serum and fat
Description
Change in FGF21 levels following nutritional intervention.
Time Frame
before and after dietary intervention
Secondary Outcome Measure Information:
Title
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
Title
Urine and serum ketosis
Time Frame
Daily during the 72-hour fast for healthy participants and participants with NAFLD
Title
Hepatic fat content
Time Frame
Before and after the 72-hour fast or hypocaloric diet in participants with NAFLD
Title
change in serum triglyceride levels
Time Frame
following fructose and glucose ingestion
Title
change in glucose and insulin levels
Time Frame
following fructose and glucose ingestion

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jody Dushay, MD
Organizational Affiliation
Beth Israel Deaconess Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States

12. IPD Sharing Statement

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Regulation of FGF21 by Nutritional Challenges

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