Protection From Acute Kidney Injury (AKI) With Basis™ Treatment

Sponsor

Mayo Clinic (Other)

Overall Status

Recruiting

CT.gov ID

NCT04342975

Collaborator

Elysium Health (Industry)

238

Enrollment

Location

Arms

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Condition or Disease	Intervention/Treatment	Phase
AKI	Drug: Nicotinamide Riboside + Pterostilbene Drug: Placebo	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

238 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

This study is a single-center, prospective, randomized, double-blinded, placebo-controlled phase II clinical trial to evaluate the efficacy of "NAD+ supplementation" with Basis™ (Nicotinamide Riboside and Pterostilbene) in preventing acute kidney injury (AKI) in patients undergoing complex aortic aneurysm repair and open aortic arch reconstruction.This study is a single-center, prospective, randomized, double-blinded, placebo-controlled phase II clinical trial to evaluate the efficacy of "NAD+ supplementation" with Basis™ (Nicotinamide Riboside and Pterostilbene) in preventing acute kidney injury (AKI) in patients undergoing complex aortic aneurysm repair and open aortic arch reconstruction.

Masking:

Double (Participant, Investigator)

Primary Purpose:

Prevention

Official Title:

A Phase II, Randomized, Double-blinded, Placebo-controlled Clinical Trial to Evaluate the Efficacy of BASIS™ (Nicotinamide Riboside and Pterostilbene) Treatment for Kidney Protection in Patients Treated by Complex Aortic Aneurysm Repair and Aortic Arch Reconstruction

Actual Study Start Date :

Dec 1, 2020

Anticipated Primary Completion Date :

Oct 1, 2023

Anticipated Study Completion Date :

Dec 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Basis The investigational product, Basis™, contains a synthetic NR that is nature-identical to naturally-occurring NR, does not induce flushing or pruritus and has no effect on lipid levels. Also contains Pterostilbene (Ptero) that is a stilbenoid compound, characterized by two aromatic rings connected by a methylene bridge backbone, and it has two methoxy groups and one hydroxyl group extending from the aromatic rings.	Drug: Nicotinamide Riboside + Pterostilbene It will be administered a total of 1000 mg/day of NR and 200 mg/day of Ptero in a regimen of 4 capsules of Basis™ (each capsule 125 mg of NR and 25 mg of Ptero) 2 times a day by mouth for 2 weeks before surgery and 6 weeks after surgery. Each intake has to be apart from each other by, at least, 6 hours of interval. Other Names: Basis
Placebo Comparator: Placebo Correspondent placebo, a capsule not containing the active component.	Drug: Placebo The correspondent placebo will be administered in a regimen of 4 capsules 2 times a day by mouth for 2 weeks before surgery and 6 weeks after surgery. Each intake has to be apart from each other by, at least, 6 hours of interval.

Arm

Intervention/Treatment

Active Comparator: Basis

The investigational product, Basis™, contains a synthetic NR that is nature-identical to naturally-occurring NR, does not induce flushing or pruritus and has no effect on lipid levels. Also contains Pterostilbene (Ptero) that is a stilbenoid compound, characterized by two aromatic rings connected by a methylene bridge backbone, and it has two methoxy groups and one hydroxyl group extending from the aromatic rings.

Drug: Nicotinamide Riboside + Pterostilbene

It will be administered a total of 1000 mg/day of NR and 200 mg/day of Ptero in a regimen of 4 capsules of Basis™ (each capsule 125 mg of NR and 25 mg of Ptero) 2 times a day by mouth for 2 weeks before surgery and 6 weeks after surgery. Each intake has to be apart from each other by, at least, 6 hours of interval.

Other Names:

Basis

Placebo Comparator: Placebo

Correspondent placebo, a capsule not containing the active component.

Drug: Placebo

The correspondent placebo will be administered in a regimen of 4 capsules 2 times a day by mouth for 2 weeks before surgery and 6 weeks after surgery. Each intake has to be apart from each other by, at least, 6 hours of interval.

Outcome Measures

Primary Outcome Measures

AKI [6 months]
The primary endpoint will be change in incidence of AKI measured by estimated glomerular filtration rate (eGFR) using the RIFLE criteria.

Secondary Outcome Measures

Myocardial infarction [6 months]
The secondary endpoint will be change in the incidence of myocardial infarction
Bowel ischemia [6 months]
The secondary endpoint will be change in the incidence of bowel ischemia
Spinal cord injury [6 months]
The secondary endpoint will be change in the incidence of spinal cord injury
Nicotinamide Adenine Dinucleotide (NAD), Nicotinamide Mononucleotide (NMN), and Nicotinamide Riboside (NR) [6 months]
NAD, NMN, NR levels in peripheral blood mononuclear cells (PBMCs)
Tissue Inhibitor of Metalloproteinases 2 (TIMP2), Kidney Injury Molecule 1 (KIM-1), Insulin-like Growth Factor-binding Protein 7 (IGFBP7) [6 months]
TIMP2, KIM-1, IGFBP7 levels in urine
Quinolinate and Tryptophan [6 months]
Quinolinate and Tryptophan levels in urine

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

A patient may be included in the study if the following conditions are present:

Male or female;
Age > 18 years old;
Patients who match the criteria for indication of elective open aortic arch replacement or repair:
Total arch;
Non-total arch;
Patients who match the criteria for indication of elective complex aortic aneurysm repair has to respect the following conditions:

Patients undergoing complex aortic aneurysm open reconstruction with a suprarenal clamp; i. thoracoabdominal aortic aneurysms Crawford extent I to IV ;

abdominal aortic aneurysms of juxtarenal, pararenal, or paravisceral type; b. For endovascular approach: i. patients with pararenal or thoracoabdominal aortic aneurysms Crawford extent I to IV and known stage III or IV of chronic kidney disease (CKD); ii. patients with pararenal or thoracoabdominal aortic aneurysms Crawford extent I to IV and solitary or single functioning kidney and known stage III or IV CKD;

Patients will be allowed to participate in concomitant endovascular aortic stent-graft trials and prospective cohort studies as long as these do not involve another investigational study drug.

Exclusion Criteria:

Patients must be excluded from the study if any of the following conditions are true:

5.2.1 General Exclusion Criteria

Unwilling to comply with the follow-up schedule;
Inability or refusal to give informed consent by the patient or a legally authorized representative;
Pregnant or breastfeeding;
Subject who takes multivitamins containing vitamin B3 derivatives in a dose > 200 mg/day; 5.2.2 Clinical / Laboratory Exclusion Criteria
Renal failure defined as eGFR< 15 mL/min/1.73m2
Patients in permanent Renal Replacement Therapy;
Patients with chronic liver disease: Child-Pugh score class B and C; 5.2.3 Medication Exclusion Criteria
Patients in chemotherapy scheme;
Patients taking any immunosuppressant, except for corticosteroids;
Patients taking any of these well-known P-glycoprotein substrates: digoxin, fexofenadine, indinavir, sirolimus.