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

• Status: Recruiting
• Trial end date: 2020-09-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: ScandiBio Therapeutics AB
• Collaborators: Göteborg University; Helsinki University Central Hospital; Koç University; Koç University Hospital; KTH Royal Institute of Technology; Monitor CRO; Sahlgrenska University Hospital, Sweden; University of Helsinki
• Treatments: Sorbitol; Tetrahydrofolates

Criteria

Inclusion Criteria:

• 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%)

Exclusion Criteria:

• 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

• Clinically significant TSH level outside the normal range (0.04-6 mU/L)

• Known allergy for substances used in the study

• Concomitant medication use:

1. Lipid-lowering drugs within 3 months

2. Oral antidiabetics given for insulin resistance of obesity (metformin, liraglutide etc.) within 3 months

3. Thiazide diuretics with a dose >25 mg/d

4. Postmenopausal estrogen therapy

5. Any medication acting on nuclear hormone receptors or inducing Cytochromes P450 (CYPs)

6. Self-administration of dietary supplements such as any vitamins, omega-3 products, or plant stanol/sterol products within 1 month

7. Treatment with medications known to cause fatty liver disease such as atypical neuroleptics, tetracycline, methotrexate or tamoxifen

8. Use of an antimicrobial agent in the 4 weeks preceding randomization

• Active smokers consuming >10 cigarettes/day

• Alcohol consumption over 192 grams for men and 128 grams for women per week

• Patients considered as inappropriate for this study for any reason (patients unable to undergo MRI study, noncompliance etc.)

• Subjects with Patatin-like phospholipase domain-containing protein 3( PNPLA3) I148M (homozygous for I148M)

• Women who are pregnant, are planning pregnancy, or who are breast-feeding

• Women of childbearing potential not protected by effective birth control method

• Active participation in another clinical study