Vitamin E and DHA-EE on NAFLD - Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Clinical Trial (PUVENAFLD)

NCT04198805 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 2017-1088
• Study Type: interventional
• Target: 205
• Locations: 1 country
• Sites: 15

Brief Summary

Multicenter, randomized, double-blinded, placebo-controlled clinical trial is focused on novel treatments for non-alcoholic fatty liver disease (NAFLD), the most common cause of chronic liver disease. The primary objective of the study is to determine the clinical efficacy and safety of Vitamin E \[(all-rac)-α-tocopheryl acetate\] and Omega-3 fatty acid (DHA EE) compared to placebo on reducing liver fat content in participants with NAFLD. There is currently no approved drug treatment for NAFLD or NASH. While several new targets are being evaluated, they are not sufficiently powered to provide definitive data. There is, therefore, a need for well-designed, appropriately powered efficacy (phase 2) trials to define the utility of newer therapies for NAFLD. The combination of Vitamin E and DHA may provide optimal benefit for patients with NAFLD due to their associated mechanisms of action, namely Vitamin E's antioxidant action, preventing lipid oxidation of long-chain fatty acids such as DHA and thus preventing the propagation of free radicals and ROS.

Conditions

Non-Alcoholic Fatty Liver Disease; Non-Alcoholic Fatty Liver; Non-Alcoholic Steatohepatitis

Keywords

Non-Alcoholic Fatty Liver Disease; Non-Alcoholic Fatty Liver; NAFL; NAFLD; Vitamin E; DHA

Outcome Measures

Primary Outcomes (1)

• Change in Hepatic Fat Fraction [%] Between of Vitamin E and DHA EE vs Placebo

  A change in liver fat content relative to baseline between Vitamin E and DHA EE vs placebo. This will be measured by MRI-PDFF at baseline and after 6 months of intervention (value at 6 months minus value at baseline).

  Baseline to 6 months

Secondary Outcomes (23)

• Change in Hepatic Fat Fraction [%] Between Vitamin E vs Placebo Arm

  Baseline to 6 months

• Change in Hepatic Fat Fraction [%] Between DHA EE vs Placebo Arm

  Baseline to 6 months

• Change After 6 Months of DHA EE and/ or Vitamin E Intervention in the Anthropometric Measure, Waist Circumference.

  Baseline to 6 months

• Change After 6 Months of DHA EE and /or Vitamin E Intervention in the Anthropometric Measure, Bodyweight.

  Baseline to 6 months

• Change After 6 Months of DHA EE and/ or Vitamin E Intervention in the Anthropometric Measure, Waist-to-hip Ratio .

  Baseline to 6 months

Study Arms (4)

Vitamin E (1000 mg)

ACTIVE COMPARATOR

Vitamin E (1000 mg) once daily for 6 months (1 capsule) and matching placebos (2 matched capsules) for 6 months.

Dietary Supplement: Vitamin E [(all-rac)-α-tocopheryl acetate]

DHA EE (1.89 g)

ACTIVE COMPARATOR

DHA EE (1.89 g) once daily for 6 months (2 capsules) and matching placebo for DHA EE (1 matched capsule for 6 months).

Dietary Supplement: Omega-3 fatty acid (DHA EE)

DHA EE (1.89 g) and Vitamin E (1000 mg)

ACTIVE COMPARATOR

DHA EE (1.89 g) once daily for 6 months and Vitamin E (1000 mg) once daily for 6 months.

Combination Product: Omega-3 fatty acid (DHA EE) & Vitamin E [(all-rac)-α-tocopheryl acetate]

Placebo

PLACEBO COMPARATOR

Matching soybean oil placebo (3 capsules) of all arms daily for 6 months.

Other: Placebo

Interventions

Vitamin E [(all-rac)-α-tocopheryl acetate] DIETARY_SUPPLEMENT

Vitamin E (1000 mg) once daily for 6 months (1 capsule) and matching placebos (2 matched capsules) for 6 months

Vitamin E (1000 mg)

Omega-3 fatty acid (DHA EE) DIETARY_SUPPLEMENT

DHA EE (1.89 g) once daily for 6 months (2 capsules) and matching placebo for DHA EE (1 matched capsule for 6 months)

DHA EE (1.89 g)

Omega-3 fatty acid (DHA EE) & Vitamin E [(all-rac)-α-tocopheryl acetate] COMBINATION_PRODUCT

DHA EE (1.89 g) once daily for 6 months and Vitamin E (1000 mg) once daily for 6 months

Also known as: Vitamin E [(all-rac)-α-tocopheryl acetate]

DHA EE (1.89 g) and Vitamin E (1000 mg)

Placebo OTHER

Matching soybean placebo (3 capsules) of all arms daily for 6 months.

Placebo

Eligibility Criteria

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

You may qualify if:

• Male or female gender
• ≥18 years of age
• A new diagnosis or reconfirmation of previously known fatty liver by imaging (ultrasound or CT or MRI), or by liver biopsy within ≤ 4 years
• Fibroscan CAP score \>300db
• Hepatic fat fraction ≥12% by MRI PDFF
• ALT≥ 40 U/L
• eGFR/Creatinine Clearance ≥ 60ml/min
• Participants with previously diagnosed Type 2 diabetes (up to 50% of sample): they must either be taking anti-diabetic medications, or their fasting (\>10 hours) glucose must be ≥ 100 mg/dL at the time of screening
• Stable weight (±5%) for at least 3 months
• Subjects willing and able to give written informed consent and to understand, to participant and to comply with the clinical study requirements.

You may not qualify if:

• Evidence of alternative causes of hepatic steatosis or other forms of chronic liver disease, e.g. Hep.B, Hep.C
• Evidence of acute Hepatitis A
• Serum ALT or AST ≥ 250 U/L
• Serum Alkaline Phosphatase \> 2 ULN
• Total bilirubin \> 2 ULN in the absence of Gilbert's Syndrome \[In patients with Gilbert's Syndrome, direct bilirubin must not exceed 2 ULN\]
• HbA1c≥9.5%
• Decompensated acute or chronic liver disease
• Clinical, imaging or histological evidence of cirrhosis
• Use of anti-NASH drugs (e.g. thiazolidinediones) in the 3 months prior to randomization
• Use of a non-stable dose of statins or fibrates in the 3 months prior to randomization
• Use of fish oil, algal oil or Krill oil supplements, drugs or foods fortified with omega-3s in the 2 months prior to randomization (\>200mg DHA/d and/or \>60mg EPA/d by FFQ)
• Known intolerance to vitamin E or DHA
• Malabsorption of Vit E (e.g. due to steatorrhea, chronic pancreatitis, severe cholestasis)
• Vitamin E supplementation of greater than 100 IU/day in the 3 months prior to randomization
• History of bariatric surgery (jejunoileal bypass or gastric weight loss surgery) or currently undergoing evaluation for bariatric surgery

Sponsors & Collaborators

• Naga P. Chalasani: lead
• DSM Nutritional Products, Inc.: collaborator

Study Sites (15)

Arizona Liver Health

Chandler, Arizona, 85712, United States

Location

Arizona Liver Health

Tucson, Arizona, 85712, United States

Location

Arkansas Gastroenterology

North Little Rock, Arkansas, 72117, United States

Location

Inland Empire Clinical Trials, LLC

Rialto, California, 92377, United States

Location

Integrity Clinical Research LLC

Doral, Florida, 33166, United States

Location

Indago Research and Health Center, Inc.

Hialeah, Florida, 33012, United States

Location

Florida Research Institute

Lakewood Rch, Florida, 34211, United States

Location

Advanced Pharma CR LLC

Miami, Florida, 33147, United States

Location

Med-Care Research

Miami, Florida, 33165, United States

Location

Summit Clinical Research LLC

Athens, Georgia, 30607, United States

Location

Indiana University School of Medicine

Indianapolis, Indiana, 46202, United States

Location

M3 Wake Research Associates

Raleigh, North Carolina, 27612, United States

Location

Centex Studies, Inc.

Houston, Texas, 77058, United States

Location

Liver Specialists of Texas/Mt. Olympus Medical Research

Houston, Texas, 77479, United States

Location

American Research Corporation at the Texas Liver Institute

San Antonio, Texas, 78215, United States

Location

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

Vitamin E; Fatty Acids, Omega-3

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Dietary Fats, Unsaturated; Dietary Fats; Fats; Lipids; Fatty Acids, Unsaturated; Fatty Acids; Fish Oils; Oils

Results Point of Contact

• Title: Naga Chalasani, MD
• Organization: Indiana University School of Medicine

nchalasa@iu.edu

(317) 278-0414

Study Officials

• Naga P. Chalasani, MD

  Indiana University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Dean of Research, Director of GI/Hepatology

Study Record Dates

• First Submitted: October 30, 2019
• First Posted: December 13, 2019
• Study Start: January 3, 2020
• Primary Completion: September 1, 2022
• Study Completion: September 1, 2022
• Last Updated: May 25, 2023
• Results First Posted: May 25, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: April, 2024

Locations

US (15)