NAD+ Augmentation for Acute Kidney Injury

(NACAM Trial)

Overseen By Ali Poyan Mehr, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Kaiser Permanente

Disqualifiers: Preexisting AKI, Kidney transplant, ESRD, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 3 days

304 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether niacinamide (a form of vitamin B3) can prevent acute kidney injury in patients undergoing heart surgery with a heart-lung machine. The trial compares niacinamide to a placebo, a pill that resembles the treatment but lacks active ingredients. It seeks to determine if niacinamide can protect the kidneys during surgery. Individuals scheduled for heart procedures like valve replacement or bypass surgery, who are at higher risk for heart complications, might be suitable candidates. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that niacinamide, a type of vitamin B3, might help improve kidney function. Some studies suggest it could reduce the need for dialysis or lower the risk of death in patients with severe COVID-19-related kidney problems, indicating potential safety.

However, not all studies have found clear benefits. Some research showed no significant improvement in kidney issues, and another study noted a possible decrease in urine output, which might indicate worsening kidney function.

Overall, niacinamide appears generally safe, but results regarding its effects are mixed. As this is a Phase 2 trial, scientists continue to gather information on its safety and effectiveness for people. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for acute kidney injury?

Unlike the standard treatments for acute kidney injury, which often include supportive care or dialysis, niacinamide offers a novel approach by potentially boosting NAD+ levels in the body. NAD+ is crucial for cellular energy and repair, and researchers believe that enhancing its levels could help protect and repair kidney cells more effectively. This new mechanism of action has researchers excited as it could provide a more targeted and less invasive alternative to current options, potentially improving outcomes for patients with acute kidney injury.

What evidence suggests that niacinamide might be an effective treatment for acute kidney injury?

Research has shown that niacinamide, a type of vitamin B3, might help people with sudden kidney problems, known as acute kidney injury (AKI). In studies involving patients with severe COVID-19 and AKI, those who took niacinamide were less likely to need kidney replacement treatments and showed better kidney function. This trial will provide participants with either oral niacinamide or a matched placebo to evaluate its effectiveness in preventing AKI. Niacinamide has also proven safe and effective in lowering the risk of some skin cancers and pre-cancerous spots, suggesting potential benefits for other health issues. These findings indicate that niacinamide could be a promising option to prevent AKI in patients undergoing heart surgery. ^{2 5 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults over 18 who need non-emergency heart surgery with a pump and are at high risk of heart-related complications. Eligible participants include those with valve surgeries, weak kidney function, reduced heart pumping capacity, history of heart failure or diabetes, protein in urine, anemia, previous bypass surgery or age 65+.

Inclusion Criteria

You have certain health conditions or risk factors that could make surgery risky for your heart, such as heart valve surgery, kidney function below a certain level, weak heart pumping function, history of heart failure, diabetes requiring insulin, diabetes not requiring insulin with certain kidney function test results, low red blood cell count, previous heart bypass surgery, or being 65 years or older.

Informed consent before any study-related activities

I have had heart surgery, including valve repair or replacement.

Exclusion Criteria

I have had a kidney transplant.

I am having heart surgery without using a heart-lung machine.

My kidney function was reduced before surgery, as shown by a creatinine test.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Nam 3 grams or placebo on the day of surgery and post-surgical days one and two

3 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

What Are the Treatments Tested in This Trial?

Interventions

• Niacinamide
• Placebo

Trial Overview The study tests if Niacinamide (a form of vitamin B3) can prevent acute kidney injury after on-pump cardiac surgery compared to a placebo. Participants will be randomly assigned to receive either Niacinamide or a placebo in this double-blind study where neither the patients nor the researchers know who gets which treatment.

How Is the Trial Designed?

Group I: Oral niacinamide Experimental Treatment 1 Intervention

Group II: Matched placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Kaiser Permanente

Lead Sponsor

Trials

563

Recruited

27,400,000+

Beth Israel Deaconess Medical Center

Collaborator

Trials

872

Recruited

12,930,000+

Cedars-Sinai Medical Center

Collaborator

Trials

523

Recruited

165,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

The study identified that the urinary ratio of quinolinic acid (QA) to 3-hydroxyanthranilic acid (3-OH AA) can predict acute kidney injury (AKI) in two cohorts, with AUC values of 0.749 and 0.729, indicating a moderate predictive ability.

Human proximal tubules were found to be the main site for NAD+ de novo synthesis, and a decrease in the enzyme HAAO, which is involved in this process, was linked to a higher risk of AKI, suggesting a potential biomarker for early detection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The metabolites of de novo NAD+ synthesis are a valuable predictor of acute kidney injury. Wang, Y., Guan, Y., Xie, Q., et al.[2023]

In patients undergoing cardiac bypass surgery, lower levels of urine tryptophan and kynurenine were linked to the development of acute kidney injury (AKI), indicating a potential issue with the kynurenine pathway involved in NAD+ synthesis.

Despite the expectation that nicotinamide (NAM) supplementation would improve kidney health by replenishing NAD+, it did not enhance kidney NAD+ levels or improve kidney function in mouse models of ischemic-reperfusion injury, suggesting that the effectiveness of vitamin B3 derivatives in treating kidney injury may vary and requires further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotinamide and acute kidney injury. Fontecha-Barriuso, M., Lopez-Diaz, AM., Carriazo, S., et al.[2021]

Administration of NMN, a precursor to NAD+, significantly reduced DNA damage and cellular senescence in human kidney cells exposed to harmful conditions, suggesting its protective effects against acute kidney injury (AKI).

In mouse models of ischemic AKI, NMN demonstrated antifibrotic properties, effectively preventing kidney fibrosis whether given before or during recovery, indicating its potential as a therapeutic strategy for kidney repair.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotinamide Mononucleotide Attenuates Renal Interstitial Fibrosis After AKI by Suppressing Tubular DNA Damage and Senescence. Jia, Y., Kang, X., Tan, L., et al.[2021]

A new NAD+ precursor called NMNH has been synthesized, which significantly increases NAD+ levels more effectively and rapidly than existing precursors like NMN and NR, using a unique metabolic pathway.

In studies with mice, NMNH not only caused a quick surge in NAD+ levels across various organs but also demonstrated protective effects against kidney damage from hypoxia, suggesting its potential as a therapeutic option for acute kidney injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduced nicotinamide mononucleotide is a new and potent NAD+ precursor in mammalian cells and mice. Zapata-Pérez, R., Tammaro, A., Schomakers, BV., et al.[2021]

Supplementation with nicotinamide (Nam), a precursor of NAD+, significantly reduced kidney inflammation and fibrosis in a mouse model of chronic kidney disease (CKD), suggesting it may help prevent disease progression.

Nam supplementation also decreased the buildup of harmful metabolites associated with renal failure by enhancing NAD+ levels, which supports metabolic pathways that are crucial for kidney function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotinamide Attenuates the Progression of Renal Failure in a Mouse Model of Adenine-Induced Chronic Kidney Disease. Kumakura, S., Sato, E., Sekimoto, A., et al.[2021]

In a study involving male Sprague-Dawley rats, niacin treatment before and after kidney ischemia and reperfusion significantly improved cardiac function and reduced oxidative stress, indicating its protective role during kidney injury.

The results suggest that kidney I/R injury leads to cardiac dysfunction through increased lipid peroxidation and altered energy production, while niacin helps sustain mitochondrial metabolism and PGC-1α expression, which is crucial for ATP production.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Niacin ameliorates kidney warm ischemia and reperfusion injury-induced ventricular dysfunction and oxidative stress and disturbance in mitochondrial metabolism in rats. Tai, ST., Fu, YH., Yang, YC., et al.[2018]

In a study of 167 cardiac bypass surgery patients, a significant decrease in urinary tryptophan and kynurenin was observed in those who developed acute kidney injury (AKI), indicating a potential biomarker for AKI risk.

However, supplementation with nicotinamide (NAM) did not improve kidney function or outcomes in a mouse model of ischaemic AKI, suggesting that NAM may not be an effective treatment for preventing renal damage in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The tryptophan pathway and nicotinamide supplementation in ischaemic acute kidney injury. Piedrafita, A., Balayssac, S., Mayeur, N., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35368823/

Niacinamide May Be Associated with Improved Outcomes in ... Niacinamide was associated with lower risk of RRT/death and improved creatinine trajectory among patients with severe COVID-19-related AKI.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8785722/

Niacinamide May Be Associated with Improved Outcomes ... Niacinamide may be associated with improved outcomes in COVID-19-related acute kidney injury: an observational study.

3. ahajournals.org ahajournals.org/doi/10.1161/JAHA.124.038603

Nicotinamide Riboside: A Promising Treatment for Type 1 ... Our data revealed a tendency for a decrease in urine output reflecting a potential deterioration in kidney function at day 4 and day 7 post‐MI.

4. academic.oup.com academic.oup.com/ckj/article/14/12/2453/6374450

Nicotinamide and acute kidney injury - Oxford Academic Oral NAM was also safe and effective in reducing the rates of new non-melanoma skin cancers and actinic keratoses in high-risk patients [17].

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02701127

Molecular Effects of Vitamin B3 (Niacinamide) in Acute ... This is a single center, randomized, single-blind, placebo-controlled study to evaluate the safety and biochemical effects of niacinamide on metabolic ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8690056/

Nicotinamide and acute kidney injury - PMC The lack of improvement of kidney injury is partially at odds with prior reports that did not study kidney NAD+, glomerular filtration or ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2468024924016504

Translational Research Derangement in NAD Metabolism in AKI Data shown are values for each of the acute kidney injury (AKI), no kidney injury (NoKI), and chronic kidney disease (CKD) groups. The “AKI – NoKI and “AKI ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT06521307

Impact of Nicotinamide Riboside (NR) on Kidney Function ... Increasing NAD+ with niacinamide has been shown to prevent various etiologies of experimental AKI in mice, and an early pilot study has shown both increased NAD ...