Graft Acute Kidney Injury: Vitamin B3 to Facilitate Renal Recovery In the Early Life of a Transplant

NCT05513807 | Completed Phase 3

• 1 other identifier: APHP200036
• Study Type: interventional
• Target: 204
• Locations: 1 country
• Sites: 1

Brief Summary

Delayed graft function occurs in more than 20% of kidney transplantations. It is an episode of post-ischemic acute kidney injury with long-term consequences on the allograft's function. Based on preclinical data and on a stage 1 clinical trial, the hypothesize is that an acquired defect in NAD+ biosynthesis is instrumental in delayed graft function and that a treatment with high doses of vitamin B3 (nicotinamide) will improve the early renal graft function. Thus, it is planned to recruit 204 kidney allograft recipients immediately before transplantation and randomize them to either placebo or nicotinamide treatment for 3 administrations before transplantation, immediately after it and on the next day. The efficacy of nicotinamide to foster early graft function will be evaluated by comparing the creatinine reduction ratio between the placebo and the nicotinamide treated groups. Serum will be collected before and 2 days after transplantation and urine 2 days and 3 months after transplantation to study the relationship between biological markers of NAD+ biosynthesis and nicotinamide's effect on early kidney graft function.

Conditions

Delayed Graft Function

Keywords

Kidney Transplantation; Delayed Graft Function; Niacinamide (NAM); Acute Kidney Injury; Acute Tubular Necrosis; creatinine reduction ratio; Nicotinamide Adenine Dinucleotide; Quinolinate; urinary quinolinate / tryptophane

Outcome Measures

Primary Outcomes (1)

• Efficacy of 3 doses of NAM given orally at 1g/dose immediately pre transplant and during the first 2 post-operative days of renal transplantation versus placebo, on the early graft function, assessed by CRR2.

  The primary endpoint is based on creatinine reduction ratio between days 1 and 2 (CRR2, calculated by the following formula: CRR2 (%) = (\[Cr1-Cr2\]×100)/Cr1, where Cr1 and Cr2 are the morning serum creatinine on post-operative day 1 and day 2 respectively.

  Post-Operative Day 2

Secondary Outcomes (9)

• Verify the safety profile of NAM (liver toxicity and tacrolimus trough levels to detect an interaction)

  Post-Operative Day 7

• Evaluate the effect of NAM on the rate of delayed graft function defined conventionally as the need for dialysis before POD7

  Post-Operative Day 7

• Evaluate the effect of NAM on renal graft function 3 months after transplantation

  3 months after transplantation

• Evaluate the effect of NAM on serum NAM levels (difference between NAM at POD2 and NAM at baseline)

  Post-Operative Day 2

• Evaluate the effect of NAM on the biopsy-proven rejection rate within three months after transplantation.

  3 months after transplantation

Study Arms (2)

Nicotinamide

EXPERIMENTAL

Drug: Nicotinamide treatment

Placebo

PLACEBO COMPARATOR

Drug: Placebo treatment

Interventions

Nicotinamide treatment DRUG

3g Nicotinamide orally (1g immediately pre transplant, then immediately 1g post-transplant after the recovery room and 1g 24 hours later)

Also known as: NICOBION

Nicotinamide

Placebo treatment DRUG

3g Placebo orally (1g immediately pre transplant, then immediately 1g post-transplant after the recovery room and 1g 24 hours later)

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years,
• Patients in end stage renal disease (ESRD) requiring dialysis (hemodialysis or peritoneal dialysis),
• Kidney transplant with deceased donor (brain death or cardiac death Maastricht 3),
• Affiliation to French social security ("AME" excepted),
• Written informed consent

You may not qualify if:

• Preemptive transplant,
• Pregnancy,
• Liver disease defined by the necessity for a specialized follow-up by an hepatologist (with liver biological results disturbed) or by elevated liver enzymes \> 3N (ALAT and/or gammaGT) on the day of transplantation
• Transplantation of multiple organs,
• Hypersensitivity to nicotinamide or one of excipients,
• Participation to another interventional study (RIPH1),
• Patient under legal protection measure (tutorship or curatorship) and patient deprived of freedom.

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Institut National de la Santé Et de la Recherche Médicale, France: collaborator
• Centre National de la Recherche Scientifique, France: collaborator

Study Sites (1)

Department of Renal Transplantation - Hospital Pitié Salpétrière

Paris, 75013, France

Location

MeSH Terms

Conditions

Delayed Graft Function; Acute Kidney Injury; Kidney Cortex Necrosis

Interventions

Niacinamide

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Pierre GALICHON, Doctor

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2022
• First Posted: August 24, 2022
• Study Start: January 12, 2023
• Primary Completion: February 17, 2024
• Study Completion: June 18, 2024
• Last Updated: July 10, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share

Locations

FR (1)