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

• ClinicalTrials.gov Identifier: NCT04342975
• Recruitment Status: Recruiting
• First Posted: April 13, 2020
• Last Update Posted: February 23, 2023
• Sponsor: Mayo Clinic
• Collaborator: Elysium Health
• Information provided by (Responsible Party): Bernardo C. Mendes, Mayo Clinic

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
AKI	Drug: Nicotinamide Riboside + Pterostilbene; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated 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.
• 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: December 1, 2020
• Estimated Primary Completion Date: October 2023
• Estimated Study Completion Date: October 2023

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 2 capsules of Basis™ (each capsule 250 mg of NR and 50 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 Name: 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 2 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 :

1. AKI [ Time Frame: 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 :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

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

  1. Male or female;
  2. Age > 18 years old;

  3. Patients who match the criteria for indication of elective open aortic arch replacement or repair:

     1. Total arch;
     2. Non-total arch;

  4. Patients who match the criteria for indication of elective complex aortic aneurysm repair has to respect the following conditions:

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

  5. 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

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

Contacts and Locations

Contacts

Contact: Karina S Kanamori Mendes, MD; 507-266-2173; mendes.karina@mayo.edu

Contact: Jennifer Haen; 507-538-7403; rstendovascularresearch@mayo.edu

Locations

United States, Minnesota

Mayo Clinic; Recruiting

Rochester, Minnesota, United States, 55905

Contact: Karina S Kanamori Mendes, MD

Sponsors and Collaborators

Mayo Clinic

Elysium Health

Investigators

• Principal Investigator: Bernardo Mendes, MD; Mayo Clinic

More Information

Additional Information:

Mayo Clinic Clinical Trials 

• Responsible Party: Bernardo C. Mendes, Principal Investigator, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT04342975
• Other Study ID Numbers: 18-000162
• First Posted: April 13, 2020
• Last Update Posted: February 23, 2023
• Last Verified: February 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Keywords provided by Bernardo C. Mendes, Mayo Clinic:

AKI; open vascular surgery; endovascular surgery; aortic arch reconstruction; Acute Kidney Injury

Additional relevant MeSH terms:

Acute Kidney Injury; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Niacinamide; Niacin; Nicotinic Acids; Vitamin B Complex; Vitamins; Micronutrients; Physiological Effects of Drugs; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Lipid Regulating Agents; Vasodilator Agents