Metabolic Cofactor Supplementation in Obese Patients With Non-Alcoholic Fatty Liver Disease

NCT04330326 | Completed Phase 2

• 1 other identifier: 309
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

This short-term, randomized, placebo-controlled, investigator-initiated trial aims to establish metabolic improvements in NAFLD subjects by dietary supplementation with cofactors N-acetylcysteine, L-carnitine tartrate, nicotinamide riboside and serine. Concomitant use of pivotal metabolic cofactors via simultaneous dietary supplementation will stimulate three different pathways to enhance hepatic β-oxidation and this study's hypothesis is that this will result in decreased amount of fat in the liver.

Conditions

Non-alcoholic Fatty Liver Disease (NAFLD)

Outcome Measures

Primary Outcomes (1)

• Magnetic Resonance Spectroscopy (MRS) Measurement

  The change in liver fat content as well as subcutaneous abdominal and intra-abdominal fat content between the placebo and cofactor treatment arms in NAFLD patients from baseline to 2 weeks, 6 weeks and 10 weeks.

  2 weeks, 6 weeks and 10 weeks

Secondary Outcomes (17)

• Change in body weight from baseline

  10 weeks

• ECG Measurement

  10 weeks

• Change in Blood Pressure from baseline

  10 weeks

• Change in waist and hip circumference from baseline

  10 weeks

• Change of complete blood count (number of blood cells) from baseline

  10 weeks

Study Arms (2)

Treatment Arm

EXPERIMENTAL

Subjects in active treatment will receive dietary supplementation with N-acetylcysteine, L-carnitine tartrate, nicotinamide riboside, and serine, administered as a mixture.

Drug: Metabolic Cofactor Supplementation

Placebo Arm

PLACEBO COMPARATOR

Subjects will take a mixture of placebo as powder dissolved in water by mouth.

Drug: Sorbitol

Interventions

Metabolic Cofactor Supplementation DRUG

Subjects in active treatment will receive dietary supplementation with N-acetylcysteine, L-carnitine tartrate, nicotinamide riboside, and serine, administered as a mixture. Half dosage of the co-factors will be given for two weeks (one dose taken just after dinner), and full dosage for 8 weeks (two equal doses taken just after breakfast and dinner).

Treatment Arm

Sorbitol DRUG

As placebo, sorbitol (5 g) flavored with strawberry aroma and coloring agent will be given. Sorbitol is widely used due to its solubility in water. It's approved by the U.S. Food and Drug Administration (FDA).

Placebo Arm

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women (18-70 years old)
• Body mass index \>27kg/m2
• Triglyceride levels ≤354 mg/dl and LDL chol ≤175 mg/dl
• No history of medication use for hepatic steatosis
• Increased liver fat (\>5.5%)

You may not qualify if:

• Inability or unwillingness to give written informed consent
• Systolic blood pressure \>160 mm Hg and/or diastolic blood pressure \> 105 mm Hg
• Type 1 or type 2 diabetes
• Chronic liver disease other than NAFLD (i.e. chronic infection with hepatitis C virus \[HCV\] or hepatitis B virus \[HBV\], autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, Wilson s disease, alpha-1 antitrypsin deficiency).
• Previous gastric or small bowel surgery
• Active gastric ulcer
• Inflammatory bowel disease
• ALT or AST \>3× ULN (upper limit of normal)
• Detection of cirrhosis by transient elastography or other imaging modalities
• Diarrhea (defined as more than 2 stool per day) within 7 days before enrollment
• Chronic kidney disease with an estimated glomerular filtration rate \<60 ml/min/1.73m2
• Significant cardiovascular co-morbidity (i.e. heart failure, documented coronary artery disease, valvular heart disease)
• Patients with active bronchial asthma
• Patients with phenylketonuria (contraindicated for NAC)
• Patients with histamine intolerance

Sponsors & Collaborators

• ScandiBio Therapeutics AB: lead
• Koç University: collaborator
• Koç University Hospital: collaborator
• Göteborg University: collaborator
• Sahlgrenska University Hospital: collaborator
• KTH Royal Institute of Technology: collaborator
• University of Helsinki: collaborator
• Helsinki University Central Hospital: collaborator
• Monitor CRO: collaborator

Study Sites (1)

Koç University Hospital

Istanbul, 34010, Turkey (Türkiye)

Location

Related Publications (1)

• Zeybel M, Altay O, Arif M, Li X, Yang H, Fredolini C, Akyildiz M, Saglam B, Gonenli MG, Ural D, Kim W, Schwenk JM, Zhang C, Shoaie S, Nielsen J, Uhlen M, Boren J, Mardinoglu A. Combined metabolic activators therapy ameliorates liver fat in nonalcoholic fatty liver disease patients. Mol Syst Biol. 2021 Oct;17(10):e10459. doi: 10.15252/msb.202110459.

  PMID: 34694070 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

Sorbitol

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Sugar Alcohols; Alcohols; Organic Chemicals; Carbohydrates

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: A total of 45 overweight or obese patients with NAFLD will be randomized on a 2:1 basis to the cofactor mixture or placebo.

Study Record Dates

• First Submitted: March 27, 2020
• First Posted: April 1, 2020
• Study Start: July 20, 2019
• Primary Completion: July 29, 2020
• Study Completion: May 6, 2022
• Last Updated: February 10, 2025

Record last verified: 2025-02

Locations

TU (1)