Study to Assess the Relationship Between Daily Dosing of NRPT and Changes in Liver Fat in Healthy Volunteers

Not Applicable

Completed

• Conditions: Fatty Liver
• Interventions: Other: Group 3 Placebo; Dietary Supplement: Group 1 NRPT; Dietary Supplement: Group 2 NRPT

• Registration Number: NCT03513523
• Lead Sponsor: Elysium Health

Brief Summary

The purpose of this study is to determine if there is a relationship between daily consumption of NRPT, over a six-month (26-week) period, and changes in liver fat accumulation, compared to placebo and change from Baseline in healthy volunteers. In addition, an exploratory assessment of markers of inflammation and liver fat metabolism will be examined.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-03-20
• Study Start: 2018-04-18
• Study First Submitted QC: 2018-04-19
• Study First Posted: 2018-05-01
• Primary Completion: 2020-05-10
• Study Completion: 2020-08-17
• Status Verified: 2020-10
• Last Update Submitted: 2020-10-23
• Last Update Posted: 2020-10-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 111

Inclusion Criteria

1. MRI-PDFF of at least 15%, as measured at Visit 2 (Baseline).
2. Men or women between the ages of 18 and 70 years.
3. BMI between 25.0 and 39.9 kg/m2.
4. Non-smokers (>3 months of non-smoking).
5. If on a statin regimen, history (> 1 month) of stable dose.
6. Able to understand and cooperate with study procedures, and have signed a written informed consent prior to any study procedures.

Exclusion Criteria

1. Diagnosis of NASH (Non-Alcoholic Steatohepatitis).
2. Bilirubin >2x ULN
3. Other causes of liver inflammation including Hepatitis A, B or C, HIV, confirmed or suspected cirrhosis, Wilson's disease, autoimmune hepatitis, hemochromatosis, alcoholic steatohepatitis, pancreatitis, or prescription medications known to cause liver damage, or known to be hepatotoxic. (Evidence of hepatocellular injury or hepatocyte ballooning.)
4. Subjects with a history of bariatric surgery.
5. Significant weight loss (> 5% body weight) or rapid weight loss (> 1.6kg/week), within six (6) months of the Screening Visit.
6. Current or recent (within six (6) months of the Screening Visit) history of significant gastrointestinal, renal, pulmonary, hepatic or biliary disease, endocrine diseases (Type II Diabetes permitted) or other invasive weight loss treatments.
7. Individual taking prescription or over-the-counter medications, including dietary supplements, known to alter lipid metabolism or liver function, within four (4) weeks of randomization.
8. Use of supplements containing pterostilbene, resveratrol, nicotinamide, or niacin, or consumption of red wine (more than 8 oz. per week) or blueberries (more than one serving per week).
9. Pregnant or lactating women or women of childbearing potential who are not using an approved method of contraception. A woman is considered to be of childbearing potential unless she is post-hysterectomy, one or more years postmenopausal, or one or more years following tubal ligation.
10. History of significant cardiovascular or coronary heart disease (CVD or CHD, respectively) as defined as having had a coronary artery bypass procedure, coronary stent or angioplasty, or myocardial infarction in the previous six (6) months.
11. History of cancer, other than non-melanoma skin cancer and basal cell carcinoma, within the previous five years.
12. Poorly controlled or uncontrolled hypertension (systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥95 mmHg).
13. Recent history of prolonged alcohol (>3 months) use (within past six (6) months) or excessive alcohol use, defined as >14 drinks per week (one drink = 12 oz. beer, 4 oz. wine, 1.5 oz. hard liquor).
14. Exposure to any investigational agent within four (4) weeks or five (5) half-lives, prior to the Screening Visit.
15. Subjects planning to undergo surgery during the study period or up to 1 month after the study
16. Any serious psychiatric disease or disorder, which, in the opinion of the investigator, would preclude the subject from participating in the study.
17. Any known intolerance to the investigational ingredients of this investigational product.
18. Has a condition the Investigator believes would interfere with the evaluation of the subject, or may put the subject at undue risk during the course of the study, including potentially abnormal lab results, due to a traumatic event.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Group 3: Placebo	Group 3 Placebo	Placebo capsules contain microcrystalline cellulose, silicon dioxide and magnesium stearate
Group 1: 1X dose of NRPT	Group 1 NRPT	250 mg of NR and 50 mg of PT
Group 2: 2X dose of NRPT	Group 2 NRPT	500 mg of NR and 100 mg of PT

Primary Outcome Measures

Name	Time	Method
Change in Fatty Liver Index	6 months	Change from Baseline in Fatty Liver Index (FLI) will be evaluated within each subject and compared between treatment groups.; FLI: = (e\^0.953\*loge (triglycerides) + 0.139\*BMI + 0.718\*loge (GGT) + 0.053\*waist circumference - 15.745) / (1 + e\^0.953\*loge (triglycerides) + 0.139\*BMI + 0.718\*loge (GGT) + 0.053\*waist circumference - 15.745) \* 100.
Change in Hepatic Fat Fraction	6 months	Change from Baseline in mean percent HFF across all nine Couinaud segments will be evaluated within each subject and compared between treatment groups.
Change in liver fat content	6 months	To determine if there is a dose effect of NRPT on changes from baseline in liver fat content compared to placebo, as determined by MRI-PDFF.
Change in Insulin Resistance (HOMA-IR)	6 months	Change from Baseline in HOMA-IR will be evaluated within each subject and compared between treatment groups.; HOMA-IR: = (\[glucose x insulin\]/450) For this measure, the comparison is between the placebo and the two IP groups at end-of-study

Secondary Outcome Measures

Name	Time	Method
Safety: LFT's	6 months	To determine the safety of NRPT as measured by change in liver function tests (AST U/L, ALT U/L, GGT U/L, Alk Phos U/L) from baseline.
Safety: Adverse Events	6 months	To determine the safety of NRPT as measured by number of adverse events and serious adverse events.

Trial Locations

Locations (9)

Altus Research, Inc.; 🇺🇸 Lake Worth, Florida, United States

Legacy Clinical Solutions: Sensible Healthcare, LLC; 🇺🇸 Ocoee, Florida, United States

IMIC, Inc; 🇺🇸 Palmetto Bay, Florida, United States

Barrett Clinic, P.C.; 🇺🇸 La Vista, Nebraska, United States

Lenus Research & Medical Group; 🇺🇸 Sweetwater, Florida, United States

Trial Management Associates, LLC; 🇺🇸 Wilmington, North Carolina, United States

Indago Research and Health Center; 🇺🇸 Hialeah, Florida, United States

Lone Star Research Center; 🇺🇸 Miami, Florida, United States

Med-Care Research Corp; 🇺🇸 Miami, Florida, United States