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

• ClinicalTrials.gov Identifier: NCT03513523
• Recruitment Status: Completed
• First Posted: May 1, 2018
• Last Update Posted: October 26, 2020
• Sponsor: Elysium Health
• Collaborator: Nutrasource Pharmaceutical and Nutraceutical Services, Inc.
• Information provided by (Responsible Party): Elysium Health

Tracking Information

• First Submitted Date: March 20, 2018
• First Posted Date: May 1, 2018
• Last Update Posted Date: October 26, 2020
• Actual Study Start Date: April 18, 2018
• Actual Primary Completion Date: May 10, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 1, 2018)

• Change in Fatty Liver Index [ Time Frame: 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 [ Time Frame: 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 Insulin Resistance (HOMA-IR) [ Time Frame: 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
• Change in liver fat content [ Time Frame: 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.

Original Primary Outcome Measures (submitted: April 19, 2018)

• Change in Fatty Liver Index [ Time Frame: 6 months ]
  Change from Baseline in FLI will be evaluated within each subject and compared between treatment groups.
• Change in Hepatic Fat Fraction [ Time Frame: 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 Insulin Resistance (HOMA-IR) [ Time Frame: 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
• Change in liver fat content [ Time Frame: 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.

Current Secondary Outcome Measures (submitted: May 1, 2018)

• Safety: Adverse Events [ Time Frame: 6 months ]
  To determine the safety of NRPT as measured by number of adverse events and serious adverse events.
• Safety: LFT's [ Time Frame: 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.

Original Secondary Outcome Measures (submitted: April 19, 2018)

• Safety: Adverse Events [ Time Frame: 6 months ]
  To determine the safety of NRPT as measured by number of adverse events and serious adverse events.
• Safety: LFT's [ Time Frame: 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

Current Other Pre-specified Outcome Measures (submitted: April 19, 2018)

Exploratory: Change in Inflammatory Marker (hsCRP) [ Time Frame: 6 months ]

Change from Baseline in hsCRP will be evaluated within each subject and compared between treatment groups.

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Study to Assess the Relationship Between Daily Dosing of NRPT and Changes in Liver Fat in Healthy Volunteers
• Official Title: A Randomized, Double-Blind, Double-Dummy, Placebo-Controlled Study to Assess the Relationship Between Daily Dosing of NRPT and Changes in Liver Fat in Healthy Volunteers
• 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 Provided
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Factorial Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Fatty Liver

Intervention

• Dietary Supplement: Group 1 NRPT
  Two capsules of NRPT and two placebo will be taken once daily in the morning for 26 weeks. Each NRPT capsule will contain 125 mg NR and 25 mg PT.
• Dietary Supplement: Group 2 NRPT
  Four capsules of NRPT will be taken once daily in the morning for 26 weeks. Each NRPT capsule will contain 125 mg NR and 25 mg PT.
• Other: Group 3 Placebo
  Four placebo capsules will be taken once daily in the morning for 26 weeks.

Study Arms

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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 4, 2019): 111
• Original Estimated Enrollment (submitted: April 19, 2018): 105
• Actual Study Completion Date: August 17, 2020
• Actual Primary Completion Date: May 10, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03513523
• Other Study ID Numbers: ELYS-170004-FL-PR
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Elysium Health
• Original Responsible Party: Same as current
• Current Study Sponsor: Elysium Health
• Original Study Sponsor: Same as current
• Collaborators: Nutrasource Pharmaceutical and Nutraceutical Services, Inc.

Investigators

• Principal Investigator: Oliver Chen, PhD; Biofortis Clinical Research, Inc.

• PRS Account: Elysium Health
• Verification Date: October 2020