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

Fatty Liver Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03513523
• Other study ID #: ELYS-170004-FL-PR
• Status: Completed
• Phase: N/A
• Start date: April 18, 2018
• Est. completion date: August 17, 2020

Study information

• Verified date: October 2020
• Source: Elysium Health
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 111
• Est. completion date: August 17, 2020
• Est. primary completion date: May 10, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• 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.
• 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.

Locations

Country	Name	City	State
United States	Indago Research and Health Center	Hialeah	Florida
United States	Barrett Clinic, P.C.	La Vista	Nebraska
United States	Altus Research, Inc.	Lake Worth	Florida
United States	Lone Star Research Center	Miami	Florida
United States	Med-Care Research Corp	Miami	Florida
United States	Legacy Clinical Solutions: Sensible Healthcare, LLC	Ocoee	Florida
United States	IMIC, Inc	Palmetto Bay	Florida
United States	Lenus Research & Medical Group	Sweetwater	Florida
United States	Trial Management Associates, LLC	Wilmington	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Elysium Health	Nutrasource Diagnostics Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Exploratory: Change in Inflammatory Marker (hsCRP)	Change from Baseline in hsCRP will be evaluated within each subject and compared between treatment groups.	6 months
Primary	Change in Fatty Liver Index	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.	6 months
Primary	Change in Hepatic Fat Fraction	Change from Baseline in mean percent HFF across all nine Couinaud segments will be evaluated within each subject and compared between treatment groups.	6 months
Primary	Change in Insulin Resistance (HOMA-IR)	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	6 months
Primary	Change in liver fat content	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.	6 months
Secondary	Safety: Adverse Events	To determine the safety of NRPT as measured by number of adverse events and serious adverse events.	6 months
Secondary	Safety: LFT's	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.	6 months