Regulation of FGF21 by Nutritional Challenges

NCT00968747 | Completed

• 1 other identifier: 2009P-000073
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Fibroblast Growth Factor 21 levels in serum and fat

  Change in FGF21 levels following nutritional intervention.

  before and after dietary intervention

Secondary Outcomes (5)

• Polymerase 1 and Transcript Release Factor levels in fat

  Prior to fasting and at the end of the 72-hour fast in healthy participants and participants with NAFLD

• Urine and serum ketosis

  Daily during the 72-hour fast for healthy participants and participants with NAFLD

• Hepatic fat content

  Before and after the 72-hour fast or hypocaloric diet in participants with NAFLD

• change in serum triglyceride levels

  following fructose and glucose ingestion

• change in glucose and insulin levels

  following fructose and glucose ingestion

Study Arms (4)

Fasting (Healthy).

EXPERIMENTAL

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

Fasting (NAFLD)

EXPERIMENTAL

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

Hypocaloric diet (NAFLD)

EXPERIMENTAL

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

Oral carbohydrate challenge

EXPERIMENTAL

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

Interventions

Fasting BEHAVIORAL

Participants will fast for 72 hours and may consume only water and vitamins.

Fasting (Healthy).

Diet BEHAVIORAL

Participants will follow a low-calorie diet until they lose 3-5% of their body weight.

Hypocaloric diet (NAFLD)

oral carbohydrate challenge DIETARY_SUPPLEMENT

Participants will fast for 16 hours and then drink a beverage containing glucose, fructose or a mixture of both

Oral carbohydrate challenge

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Beth Israel Deaconess Medical Center: lead

Study Sites (1)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Fasting; Non-alcoholic Fatty Liver Disease; Platelet Glycoprotein IV Deficiency

Interventions

Angptl4 protein, mouse; Diet

Condition Hierarchy (Ancestors)

Feeding Behavior; Behavior; Fatty Liver; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Study Officials

• Jody Dushay, MD

  Beth Israel Deaconess Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: July 31, 2009
• First Posted: August 31, 2009
• Study Start: July 1, 2009
• Primary Completion: July 31, 2023
• Study Completion: July 31, 2023
• Last Updated: August 14, 2023

Record last verified: 2023-08

Locations

US (1)