NAD Augmentation for Diabetic Kidney Disease

(DKD Trial)

Overseen By Nancy Latham, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Brigham and Women's Hospital

Must be taking: ACE inhibitors, ARBs

Disqualifiers: Cardiovascular event, Substance use, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

140 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a new treatment, Nicotinamide Mononucleotide (NMN), can improve diabetic kidney disease by reducing a marker in the urine. Participants will receive either the NMN treatment or a placebo (a harmless pill with no active ingredients) for comparison. Individuals with type 2 diabetes who take medication and meet specific kidney function criteria are suitable candidates for this study. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, providing participants an opportunity to contribute to significant medical advancements.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if your UACR is over 300 mg/g creatinine, you must be using an ACE inhibitor or an ARB. It's best to discuss your current medications with the trial team.

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

Research has shown that nicotinamide mononucleotide (NMN), the main ingredient in MIB-626, is safe for humans. One study found that participants who took 1250 mg of NMN daily for four weeks experienced no major side effects. This study included healthy adult men and women, demonstrating that NMN is well-tolerated across different groups.

Another study found that NMN can address aging issues, such as DNA damage and cell stress. Although these issues are not directly linked to diabetic kidney disease, they confirm NMN's safety.

In animal studies, NMN protected diabetic mice from kidney damage. While mice differ from humans, these results are promising for those with diabetic kidney disease.

In summary, NMN has a strong safety record in both humans and animals, suggesting that MIB-626 is likely well-tolerated. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for diabetic kidney disease?

Unlike the standard treatments for diabetic kidney disease, which often involve blood pressure management and glucose control medications, MIB 626 is focused on cellular health. This investigational product uses a compound called NMN (nicotinamide mononucleotide) to boost levels of NAD+, a molecule that plays a critical role in energy production and cell repair. Researchers are excited because increasing NAD+ levels could potentially improve kidney function at a cellular level, offering a novel approach that targets the underlying causes of kidney damage rather than just managing symptoms.

What evidence suggests that NMN might be an effective treatment for diabetic kidney disease?

Research has shown that NMN, a key component of MIB-626, may help treat diabetic kidney disease. Participants in this trial may receive MIB-626, which contains NMN. Studies have found that NMN can protect kidney cells in diabetic mice, improving kidney structure and function. NMN raises NAD+ levels, which are often lower in diabetic kidneys. This increase in NAD+ is linked to a reduction in the urinary albumin to creatinine ratio (UACR), an important indicator of diabetic kidney disease. Overall, these findings suggest that NMN could help reduce kidney damage caused by diabetes. ^{1 5 6 7 8}

Who Is on the Research Team?

Shalender Bhasin, MD

Principal Investigator

Brigham and Women's Hospital

Are You a Good Fit for This Trial?

This trial is for adults with Type 2 Diabetes and Diabetic Kidney Disease. Participants must have a certain level of kidney function, controlled blood sugar levels, and be on specific medications if their urine shows high protein levels. Pregnant women or those planning pregnancy soon cannot join. People with recent serious health events, severe psychiatric conditions, very high BMI, substance abuse history, or who've been in other drug trials recently are excluded.

Exclusion Criteria

I have not had a major heart problem in the last 3 months.

You have had a problem with alcohol or drugs in the last 2 years.

Your urine test shows a high level of protein first thing in the morning.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either 1000 mg NMN or placebo twice daily to assess improvements in DKD over a 6-month period

24 weeks

Regular visits for monitoring and assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment, with a focus on sustained NAD levels

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Investigational Product - MIB 626
• Placebo

Trial Overview

The study tests MIB 626 (a form of NMN) to see if it can improve kidney function in diabetic patients better than a placebo. It's randomized and double-blind meaning neither the researchers nor participants know who gets the real treatment versus a fake one (placebo). Each participant takes either MIB 626 or placebo twice daily.

How Is the Trial Designed?

Group I: Investigational Product - MIB 626 Active Control 1 Intervention

The MIB-626 will be a GMP-grade microcrystalline solid NMN mixed with inert excipients (including microcrystalline cellulose) and compressed into tablets at a dose strength of 500 mg per tablet, enabling administration of the 1,000 mg twice daily using two tablets taken twice daily.

Group II: Placebo Placebo Group 1 Intervention

Participants randomized to placebo will receive Matching placebo tablets will be provided by Metro International Biotech, LLC.

Who Is Running the Clinical Trial?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

Boston Medical Center

Collaborator

Trials

410

Recruited

890,000+

Published Research Related to This Trial

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]

Nicotinamide mononucleotide (NMN) significantly enhances insulin secretion in RIN-m5f cells, especially when combined with repaglinide, indicating its potential role in improving insulin response.

NMN treatment increases the mRNA expression of the transcription factor PDX-1, which is crucial for insulin secretion, while not significantly affecting the expression of FoxO1, suggesting a targeted mechanism of action for NMN in insulin regulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of nicotinamide mononucleotide on insulin secretion and gene expressions of PDX-1 and FoxO1 in RIN-m5f cells. Sheng, F., Ren, X., Dai, X., et al.[2022]

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]

Modified-release nicotinamide (NAMR) significantly reduced serum phosphate levels in hemodialysis patients over the first 24 weeks, but this effect was not maintained at 52 weeks, indicating potential issues with long-term efficacy.

The treatment was associated with increased risks of side effects such as thrombocytopenia, pruritus, anemia, and diarrhea, as well as herpes zoster occurring only in NAMR patients, highlighting the need for careful monitoring of safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modified-release nicotinamide for the treatment of hyperphosphataemia in haemodialysis patients: 52-week efficacy and safety results of the phase 3 randomized controlled NOPHOS trial. Ketteler, M., Wiecek, A., Rosenkranz, AR., et al.[2023]

The synthetic form of β-nicotinamide mononucleotide (NMN-C®) was found to be safe in a study involving acute and subchronic toxicity tests, with no mutagenic or genotoxic effects observed.

In a 90-day study with doses up to 1500 mg/kg/day, NMN-C® did not show any adverse effects, establishing a No-Observable Adverse Effect Level (NOAEL) of ≥1500 mg/kg/day, indicating its potential safety for short to intermediate-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety evaluation after acute and sub-chronic oral administration of high purity nicotinamide mononucleotide (NMN-C®) in Sprague-Dawley rats. Cros, C., Cannelle, H., Laganier, L., et al.[2021]

Trimethoprim significantly inhibits the transport of metformin and NMN through renal cation transporters, leading to increased plasma levels of metformin by 29.5% and decreased renal clearance of both drugs.

The study suggests that NMN can serve as a useful probe for predicting drug interactions involving renal cation transporters, based on findings from a clinical trial with 12 healthy volunteers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

N(1)-methylnicotinamide as an endogenous probe for drug interactions by renal cation transporters: studies on the metformin-trimethoprim interaction. Müller, F., Pontones, CA., Renner, B., et al.[2018]

In a double-blind, placebo-controlled study involving 32 overweight or obese adults aged 55-80, the microcrystalline formulation MIB-626 was found to be safe and well-tolerated, with no significant differences in adverse events compared to placebo.

MIB-626 significantly increased blood levels of nicotinamide mononucleotide (NMN) and nicotinamide adenine dinucleotide (NAD) in a dose-dependent manner, suggesting its potential to enhance NAD metabolism and support healthspan.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MIB-626, an Oral Formulation of a Microcrystalline Unique Polymorph of β-Nicotinamide Mononucleotide, Increases Circulating Nicotinamide Adenine Dinucleotide and its Metabolome in Middle-Aged and Older Adults. Pencina, KM., Lavu, S., Dos Santos, M., et al.[2023]

Oral supplementation of nicotinamide mononucleotide (NMN) at 250 mg/day for 24 weeks was found to be safe for older male patients with diabetes, with no severe adverse events reported.

Despite the safety of NMN, the study showed no significant improvements in grip strength or walking speed compared to the placebo group, although there were indications of reduced frailty and changes in retinal thickness that warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of nicotinamide mononucleotide on older patients with diabetes and impaired physical performance: A prospective, placebo-controlled, double-blind study. Akasaka, H., Nakagami, H., Sugimoto, K., et al.[2023]

In a study of 66 children with newly diagnosed type 1 diabetes, low doses of nicotinamide (1-2 mg/kg per day) were associated with significantly lower insulin requirements over a 24-month period compared to a control group of 37 children who did not receive the treatment.

The findings suggest that nicotinamide therapy may help prolong the honeymoon period in pediatric patients with type 1 diabetes, indicating a potential benefit in managing the disease early after diagnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of nicotinamide on newly diagnosed type 1 diabetic children. Kamal, M., Abbasy, AJ., Muslemani, AA., et al.[2013]

A study involving 31 healthy adults showed that daily oral administration of 1250 mg of β-NMN for 4 weeks is safe and well-tolerated, with no significant adverse effects reported.

The research indicates that β-NMN does not cause harmful changes in various health parameters, suggesting its potential for further exploration in age-related disease prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety evaluation of β-nicotinamide mononucleotide oral administration in healthy adult men and women. Fukamizu, Y., Uchida, Y., Shigekawa, A., et al.[2022]

Citations

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pmc.ncbi.nlm.nih.gov

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Nicotinamide mononucleotide protects against diabetic ...

Collectively, these in vivo data demonstrate that NMN was effective in alleviating podocyte injury in diabetic mice, and the protective ...

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reporter.nih.gov

reporter.nih.gov/search/-RdACYIeT0WW6iAuomvfVA/project-details/10906074

NAD Augmentation to Treat Diabetic Kidney Disease

These data support the hypothesis that NAD augmentation by NMN administration will reduce urinary albumin to creatinine ratio (UACR), a hallmark of DKD that is ...

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frontiersin.org

frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2024.1384953/full

Unraveling the nexus of NAD+ metabolism and diabetic ...

Our study demonstrated KMO of NAD+ de novo synthesis pathway was decreased in diabetic kidney and might be responsible for NAD+ reduction in diabetic kidneys.

4.

researchgate.net

researchgate.net/publication/396575462_Nicotinamide_mononucleotide_protects_against_diabetic_nephropathy_via_IL-6Rab5-mediated_crosstalk_between_proximal_tubular_epithelial_cells_and_podocytes

Nicotinamide mononucleotide protects against diabetic ...

Nicotinamide mononucleotide protects against diabetic nephropathy via IL-6/Rab5-mediated crosstalk between proximal tubular epithelial cells and ...

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nmn.com

nmn.com/news/nmn-diabetic-kidney-disease

Mouse Study Shows NMN Can Prevent Diabetic Kidney ...

Highlights. · Diabetic mice treated with NMN for two weeks showed improved kidney structure and function, increasing survival.

6.

nature.com

nature.com/articles/s41598-022-18272-y

Safety evaluation of β-nicotinamide mononucleotide oral ...

Our results indicate that β-NMN is safe and well-tolerated in healthy adult men and women an oral dose of 1250 mg once daily for up to 4 weeks.

7.

sciencedirect.com

sciencedirect.com/science/article/pii/S2161831323013595

The Safety and Antiaging Effects of Nicotinamide ...

NMN supplementation increases NAD + concentration and could mitigate aging-related disorders such as oxidative stress, DNA damage, neurodegeneration, and ...

8.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8259649/

Pre-emptive Short-term Nicotinamide Mononucleotide ...

Our results suggest NAD+ and Sirt1 deficits in mice with diabetes contribute to kidney damage susceptibility. Short-term NMN treatment rescued the diabetic ...