RCT of Caloric Restriction vs. Alternate-Day Fasting in Non-Alcoholic Fatty Liver Disease

NCT03365531 | Terminated

• 2 other identifiers: IRB201701956OCR16250
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

Non-alcoholic fatty liver disease (NAFLD) in patients with diabetes (T2DM) is increasing in prevalence and can lead to cirrhosis. Lifestyle intervention with caloric restriction (CR) is the cornerstone of treatment but remission is variable. Alternatively, the PI has shown alternate day fasting (ADF) is safe and well tolerated in obese patients and there might be additional beneficial effects. The objective is to combine the expertise of the PI with this novel intervention and the expertise of Dr. Cusi in NAFLD to explore the effects of ADF vs CR in patients with NAFLD and T2DM to test the following hypotheses: H1: In patients with NAFLD and T2DM, the ADF intervention will result in more favorable metabolic changes than CR: H1a: Hepatic triglyceride by MRS will decrease more with ADF than CR (Primary Outcome) and remain lower following a period of free living H1b: There will be greater improvements in glucose homeostasis following ADF vs CR H1c: There will be greater improvement in lipid metabolism following ADF vs CR and changes in ketone metabolism will predict changes in hepatic triglyceride content H2: ADF will have similar safety and tolerability and result in a similar degree of weight loss in participants with NAFLD and DM compared to CR

Conditions

NAFLD; Obesity; Diabetes Mellitus, Type 2

Keywords

fasting

Outcome Measures

Primary Outcomes (1)

• Hepatic Triglyceride by MRS

  To determine changes in hepatic triglyceride by MRS after 4 weeks of ADF (Primary outcome) and after 4 weeks of ad lib diet

  Baseline up to 8 weeks

Secondary Outcomes (9)

• Changes in Glucose Homeostasis

  Baseline through 4 weeks

• Changes in whole body lipid metabolism - Adipose tissue insulin sensitivity by AdipoIR and fasting and postprandial free fatty acid excursion

  Baseline through 4 weeks

• Safety of ADF -Liver Magnetic Resonance Spectroscopy (MRS)

  Baseline through 4 weeks

• Safety of ADF -Fibroscan.

  Baseline through 4 weeks

• Safety of ADF - blood

  Baseline through 4 weeks

Study Arms (2)

Alternate Daily Fasting (ADF)

EXPERIMENTAL

Participants randomized to the ADF group will alternate between a day of ad lib feeding and a day of nearly no energy intake. Participants will be prescribed a core diet for feeding days that meets 110% of their estimated calorie needs within the fixed macronutrient distribution of 50% CHO, 20% PRO, and 30% FAT. In accordance with the ad lib feeding protocol, optional modules of similar macronutrient content will be prescribed, each providing an additional 200 kcals. Meal timing will not be restricted on these days. On fasting days, participants will be asked to consume 16 oz. of G2 Gatorade (40 kcal) in the morning and then only water or non-caloric beverages for the rest of the day.

Other: Alternate Daily Fasting (ADF)

Caloric Restriction

ACTIVE COMPARATOR

Participants randomized to the CR group will consume a diet of fixed energy designed to yield a 500 kcal/d deficit with a macronutrient distribution of 50% CHO, 20% PRO, and 30% FAT. Meal timing and caloric distribution will not be restricted.

Other: Caloric Restriction (CR)

Interventions

Alternate Daily Fasting (ADF) OTHER

See ADF arm for details

Alternate Daily Fasting (ADF)

Caloric Restriction (CR) OTHER

See CR arm for details

Caloric Restriction

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient must give study-specific informed consent on an IRB-approved consent prior to any research related procedures or study treatment.
• Patient must be at least 18 years at the time of consent Adenocarcinoma of the prostate with AJCC Clinical Stage T1to T3b disease with histological evaluation via biopsy or repeat biopsy within 12 months prior to registration. Refer to Appendix IV for clarification on study eligibility and AJCC stage group.
• Patients must undergo a pretreatment diagnostic MRI of the prostate on a 1.5T to 3T Tesla machine within 6 months prior to study registration.
• A focal IPT must be visible on MRI within the prostate and/or seminal vesicles and this MRI must be obtained within 6 months of planning CT scan.
• A biopsy of the dominant lesion is recommended but not required. If an ultrasound guided sextant biopsy was positive for prostatic adenocarcinoma in the area of the MRI identified intraprostatic lesion, this will be acceptable and another guided biopsy targeting the MRI identified disease will not be necessary.
• Patients with at least one of the following high-risk factors: cT3a-T3b OR Gleason 9-10 OR PSA \> 30 OR more than 1 high-risk factors must be present: clinical stage of T3, Gleason score 8-10, or PSA 20 ng/ml or greater.
• Hemoglobin must be ≥ 10 g/ml within 4 months prior to registration.
• Zubrod performance status must be 0-1 within 4 months prior to registration.
• If patient has child-producing potential, they must be willing to use medically acceptable contraception during treatment and must be advised to use it for at least 1 year thereafter. This is not applicable if the patient is not sexually active or has had a vasectomy. Please document as such.
• Patients must be able to start treatment within 16 weeks of registration.

You may not qualify if:

• T4 prostate disease on CT, MRI, or physical exam.
• Patients unable to undergo MRI of the prostate.
• Patients with a greater than 25% change in prostate volume from the pretreatment MRI of the prostate demonstrating the IPT and the treatment planning MRI. Patients in this case must undergo a repeat diagnostic MRI on a 1.5T to 3.0T Tesla machine and an IPT must still be visible.
• IPT that is more than 75% of the prostate volume when measured on the CT simulation scan.
• Evidence of distant metastasis (M1).
• Patients with positive nodes on cross-sectional imaging.
• Previous prostate cancer local treatment including prostatectomy, hyperthermia, high intensity focused ultrasound, brachytherapy, external-beam radiation therapy, and/or cryotherapy.
• Prior pelvic radiation therapy.
• No prior myocardial infarction within the last 6 months, congestive heart failure, or end stage renal disease.
• Active inflammatory bowel disease (diverticulitis, Crohn's disease, ulcerative colitis) affecting the rectum.
• Bilateral hip replacement
• Prior intrapelvic surgery. This includes the following:Bladder surgery,Transrectal or rectal surgery other than prostate biopsy, Polypectomy or hemorrhoid removal or banding
• Prior transurethral resection of the prostate (TURP) or laser ablation for benign prostatic hyperplasia (BPH).
• Patients receiving continuous and current anticoagulation with warfarin sodium (Coumadin), heparin sodium, clopidogrel bisulfate (Plavix), dabigatran etexilate mesylate (Pradaxa), rivaroxaban (Xarelto), apixaban (Eliquis), edoxaban (Savaysa), enoxaparin sodium (Lovenox), prasugrel (Effient), ticagrelor (Brilinta), aspirin/er dipyridamole (Aggrenox), or fondaparinux sodium (Arixtra).
• Patients with posterior or posterolateral extracapsular extension of prostate cancer. If this is present, it must resolve on diagnostic MRI after 2 to 3 months of neoadjuvant androgen deprivation therapy prior to enrollment. Refer to Appendix V for definition of extracapsular extension

Sponsors & Collaborators

• University of Florida: lead

Study Sites (1)

University of Florida

Gainesville, Florida, 32610, United States

Location

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Obesity; Diabetes Mellitus, Type 2; Fasting

Interventions

Caloric Restriction

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Feeding Behavior; Behavior

Intervention Hierarchy (Ancestors)

Diet Therapy; Nutrition Therapy; Therapeutics; Energy Intake; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Study Officials

• William T Donahoo, MD

  University of Florida

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized Controlled Trial of Caloric Restriction vs. Alternate-Day Fasting

Study Record Dates

• First Submitted: October 20, 2017
• First Posted: December 7, 2017
• Study Start: March 1, 2018
• Primary Completion: July 1, 2019
• Study Completion: July 1, 2019
• Last Updated: September 23, 2019

Record last verified: 2019-09

Locations

US (1)