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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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AKI

Intervention / Treatment
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* Drug: Nicotinamide Riboside + Pterostilbene
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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: 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; 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Basis<br>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<br>* 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.<br>* Other names: Basis;|
| Placebo Comparator: Placebo<br>Correspondent placebo, a capsule not containing the active component. | Drug: Placebo<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AKI | The primary endpoint will be change in incidence of AKI measured by estimated glomerular filtration rate (eGFR) using the RIFLE criteria. | 6 months | 

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AKI, open vascular surgery, endovascular surgery, aortic arch reconstruction, Acute Kidney Injury