A Phase 2 interventional study of Metabolic Cofactor Supplementation and Sorbitol in Non-alcoholic Fatty Liver Disease (NAFLD), sponsored by ScandiBio Therapeutics AB. Completed at 1 site in Turkey. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2025-02-10.
Sponsored by ScandiBio Therapeutics AB · Phase 2, Interventional, and Treatment
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.
In this study, investigators aim to lower liver fat content in obese patients with NAFLD by increasing the hepatic levels of pivotal metabolic cofactors via simultaneous dietary supplementation of serine, L-carnitine, N-acetylcysteine (NAC) and nicotinamide riboside (NR).
The study is based on a three-step strategy to increase the amount of fat oxidization in liver: (1) First, the investigators will include L-carnitine to enhance the transport of fatty acids across the mitochondrial membrane (by forming a long chain acetylcarnitine ester and being transported by carnitine palmitoyltransferase (CPT) I and CPT II). Carnitine also plays a role in stabilizing coenzyme A (CoA) and acetyl-CoA levels through the ability to receive or give an acetyl group. (2) Second, the investigators will include nicotinamide riboside, precursor of nicotinamide adenine dinucleotide (NAD+) to boost the level of hepatic β-oxidation of fatty acids in mitochondria. Decreased electron transport chain function combined with impaired rates of fatty acid β-oxidation leads to the accumulation of incomplete products of β-oxidation, which combined with increased levels of reactive oxygen species (ROS) contribute to insulin resistance. Furthermore, as L-carnitine, nicotinamide
riboside stimulate the transfer of fatty acids from cytosol to mitochondria.(3) Finally, they will include the two glutathione precursors serine and N-acetylcysteine to increase glutathione levels in the hepatocytes. Increased glutathione levels will also protect against free radical-mediated oxidative stress generated by the increased β-oxidation of fatty acids in mitochondria.
Previous studies showed that each agent is able to decrease liver fat amount separately and a proof-of-concept study using serine supplementation, and a phase I study using this three-step approach resulted in a significant decrease in plasma metabolites associated with liver fat without significant side effect. Concomitant use of pivotal metabolic cofactors via simultaneous dietary supplementation will stimulate three different pathways to enhance hepatic β-oxidation. The novel design with this study is to give the L-carnitine, NR, serine and NAC as a cocktail. Based on investigators' hypothesis is that this will result in decreased amount of fat in the liver.
The study population will consist of 45 male and female adult overweight and obese subjects diagnosed with NAFLD. Eligible subjects must have signed an informed consent, meet all inclusion criteria and have none of the exclusion criteria. Patients will be randomized on a 2:1 basis to the cofactor mixture or placebo.
The subjects will take a mixture of cofactors or matching placebo as powder dissolved in water by mouth. 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). Patients who can tolerate the study agents will start to take half dose of co-factors supplementation (i.e., 1 dosage daily just after dinner) for two weeks.
The active treatment duration will be 10 weeks for each subject and the total study duration is estimated as 14 months. The study comprises seven clinical visits; (1) pre-screening visit, (2) screening visit, (2) randomization visit, (3) post-treatment visit (day 14); (4) post-treatment visit (day 28); (5) post-treatment visit (day 42) and (4) end of treatment visit (day 70). At visit 1 informed consent will be signed, all procedures including clinical and physical examination, assessment of inclusion and exclusion criteria, genetic analysis and transient elastography will be done. At visit 2 and visit 7, all procedures including review of 3-day diet records, clinical and physical examination; body composition analysis with Bioelectrical Impedance Analysis (BIA), ECG evaluation, blood, urine and stool sampling for routine laboratory tests, lipidomics, metabolomics and gut microbiota analysis and magnetic resonance imaging and MR spectroscopy will be carried out. At visit 3, eligible study subjects will be randomized to active therapy or placebo groups and study agents will be dispensed as half-of therapy. At visit 4, and 6, clinical and physical examination, ECG evaluation, blood, urine and stool sampling for routine laboratory tests, lipidomics, metabolomics and gut microbiota analysis, magnetic resonance imaging and MR spectroscopy and initiation of full dose therapy (i.e. taking cocktails two times just after breakfast and dinner) will be realized. At visit 5, visit 4 and 6 will be repeated excluding magnetic resonance imaging and MR spectroscopy. After the visit 7, participants will stop taking study agents.
A subject will be considered as having completed the study if he/she has completed all assessments at the End of Treatment Visit (Visit 7) and has been followed up until 10 weeks after initiation of the study drugs.
Statistics for the primary outcome parameter will be tested by Mann-Whitney U test or t-test depending on the results of normality test. For the secondary and third outcome parameters one-way repeated measures ANOVA will be performed.
2,080 studies on the registry are indexed under Liver Diseases; 389 are open to participants now.
This study's enrollment of 32 is below the median of 50 across 1,322 interventional studies indexed under Liver Diseases.
Browse Liver Diseases studies →ScandiBio Therapeutics AB is the lead sponsor of 3 studies on the registry; 1 is open to participants now.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Concomitant medication use:
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
Subjects will take a mixture of placebo as powder dissolved in water by mouth.
Drug: Sorbitol
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).
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).
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.
Time frame: 2 weeks, 6 weeks and 10 weeks
Change in body weight from baseline
Body weight will be measured at every visit to evaluate safety of metabolic cofactor supplementation.
Time frame: 10 weeks
ECG Measurement
Change in heart rate will be measured at every visit to evaluate safety of metabolic cofactor supplementation.
Time frame: 10 weeks
Change in Blood Pressure from baseline
Systolic and Diastolic Blood Pressure will be measured at every visit to evaluate safety of metabolic cofactor supplementation.
Time frame: 10 weeks
Change in waist and hip circumference from baseline
Waist and hip circumference will be measured at every visit to evaluate safety of metabolic cofactor supplementation.
Time frame: 10 weeks
Change of complete blood count (number of blood cells) from baseline
Complete blood count includes number of blood cells. Complete blood count test will be performed to measure possible toxic effects of the metabolic cofactor supplementation on hematological system.
Time frame: 10 weeks
Change of complete blood count (hemoglobin) from baseline
Complete blood count includes concentration of hemoglobin. Complete blood count test will be performed to measure possible toxic effects of the metabolic cofactor supplementation on hematological system.
Time frame: 10 weeks
Changes in kidney function tests (creatinine, urea, uric acid) from baseline
Kidney function tests (creatinine, urea, uric acid) will be performed to measure possible toxic effects of the metabolic cofactor supplementation on kidney function.
Time frame: 10 weeks
Changes in kidney function tests (sodium, potassium) from baseline
Kidney function tests (sodium, potassium) will be performed to measure possible toxic effects of the metabolic cofactor supplementation on kidney function.
Time frame: 10 weeks
Changes in liver function tests [Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma-glutamyl transferase (GGT), Alkaline phosphatase (ALP)] from baseline
Liver function tests (ALT, AST, GGT, ALP) will be performed to measure possible toxic effects of the metabolic cofactor supplementation on liver function.
Time frame: 10 weeks
Changes in liver function tests (Total Bilirubin, and Albumin) from baseline
Liver function tests (Total Bilirubin, Albumin) will be performed to measure possible toxic effects of the metabolic cofactor supplementation on liver function.
Time frame: 10 weeks
Changes in creatinine kinase (CK) level from baseline
Creatinine kinase (CK) level will be evaluated to measure possible toxic effects of the metabolic cofactor supplementation.
Time frame: 10 weeks
Changes in blood lipid levels (total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL-C), high density lipoprotein (HDL-C)) from baseline
Blood lipid levels (total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL-C), high density lipoprotein (HDL-C)) will be evaluated to measure possible toxic effects of the metabolic cofactor supplementation.
Time frame: 2 weeks, 6 weeks and 10 weeks
Changes in blood glucose levels from baseline
Blood glucose levels will be evaluated to measure possible toxic effects of the metabolic cofactor supplementation.
Time frame: 10 weeks
Change in blood insulin level from baseline
Blood insulin level will be evaluated to measure possible toxic effects of the metabolic cofactor supplementation.
Time frame: 10 weeks
Change in thyroid-stimulating hormone (TSH) level from baseline
Thyroid-stimulating hormone (TSH) level will be evaluated to measure possible toxic effects of the metabolic cofactor supplementation.
Time frame: 10 weeks
Microbiota analysis
The change in gut microbiota between the placebo and the treatment arms in NAFLD patients. Feces and saliva samples will be collected to assess changes in gut microbiota. Instructions on specimen collection will be given during the first visit. Microbiota will be assessed using shot-gun metagenomic techniques.
Time frame: 2 weeks, 6 weeks and 10 weeks
Monitoring of adverse events
This process aiming to monitoring of adverse events of metabolic cofactor supplementation. Adverse events and serious adverse events will be monitored continuously and all adverse events that occur at any time during the study will be reported in Case Report Forms. Any symptoms of intestinal discomfort or other side effects will be carefully recorded and all study subjects will be informed to contact (by phone or text message) the investigators immediately if they experience any symptoms of discomfort or any side effects during the intervention period.
Time frame: 10 weeks
This study is completed, as verified in Feb 2025. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.