NAD Augmentation in Diabetes Kidney Disease

Study Overview
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Brief Summary
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A phase 2a trial randomized, double-blind, placebo-controlled, parallel group trial to determine whether NMN administration improves DKD, as indicated by a significantly greater reduction in UACR compared with placebo administration. Eligible participants will be randomized to receive either 1000 mg NMN or placebo twice daily.

Detailed Description
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This will be two centers, randomized, double-blind, placebo-controlled, parallel group trial to determine whether βNMN, after its daily oral administration, is associated with a greater reduction in the UACR compared to placebo. The trial will enroll community-dwelling older adults, 60 years or older, with type 2 diabetes mellitus (T2DM) and urine albumin to creatinine excretion ratio > 100 mg/ g creatinine.

Official Title
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NAD Augmentation to Treat Diabetes Kidney Disease: A Randomized Controlled Trial

Conditions
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Type2diabetes, Diabetic Kidney Disease

Intervention / Treatment
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* Drug: Investigational Product - MIB 626
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has T2DM, as indicated by any of the following: Self-report of diabetes plus the use of a prescribed diabetes medication. ICD-10 code for diabetes plus current use of a diabetes medication in the electronic medical record. HbA1c >6.4%; or 2 fasting glucose > 125 mg/dL Fasting morning UACR between 100 and 2,000 mg/g creatinine on two separate days If UACR is > 300 mg/g creatinine, must be currently using an ACE inhibitor or an ARB eGFR > 30 mL/ min / 1.73 m2 Hemoglobin A1c <9% Able to speak English or Spanish Willing and able to provide written informed consent In addition, female participants must Not be pregnant and not planning to become pregnant over the next 6 months Exclusion Criteria: Fasting morning UACR > 2,000 mg/ g creatinine Other laboratory abnormalities: Has AST or ALT > 3 times the upper limit of normal creatinine > 2.5 mg/dL Hematocrit < 0.34 or 0.50 L/L A major adverse cardiovascular event in preceding 3 months Participation in an investigational trial to evaluate pharmaceuticals or biologics within the past 3 months or 5 half-lives, whichever is shorter Hypoglycemia unawareness or other medical conditions which could jeopardize participant's safety. History of alcohol or substance use disorder or dependence (DSM 5 criteria) within the last 2 years. Major depressive disorder, bipolar disorder, schizophrenia, or current psychotic symptoms or behavioral problems that could interfere with study procedures. BMI > 42.5 kg/ m2

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This will be two center, randomized, double-blind, placebo-controlled, parallel group trial to determine whether βNMN, after its daily oral administration, is associated with a greater reduction in the UACR compared to placebo.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Investigational Product - MIB 626<br>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. | Drug: Investigational Product - MIB 626<br>* The eligible participants will be assigned to receive either NMN or placebo using concealed block randomization in a 1:1 ratio, stratified by sex (male, female), age (60 to 75, >75 years) and trial site. The randomization list will be generated by the unblinded biostatistician using the software R (www.r-project.org), and deployed in a secure, centralized web-based application accessible to study staff following confirmation of a participant's eligibility.<br>* Other names: NMN;|
| Placebo Comparator: Placebo<br>Participants randomized to placebo will receive Matching placebo tablets will be provided by Metro International Biotech, LLC. | Drug: Placebo<br>* Placebo - Participants randomized to placebo will receive Matching placebo tablets will be provided by Metro International Biotech, LLC.<br>* Other names: Placebo for NMN;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary endpoint is the change from baseline in UACR over the 6-month intervention period. | To determine whether treatment with a microcrystalline formulation of β nicotinamide mononucleotide (βNMN) in older adults with DKD improves urinary albumin to creatinine excretion ratio (UACR), compared to placebo. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the proportion of participants in the two study arms with 30% or greater reduction in UACR | In supportive analysis of the primary outcome, the investigator will compare the proportion of participants in the two study arms with 30% or greater reduction in UACR | 6 months | 
| Assess the change from baseline over the 6-month intervention period in biomarkers of kidney injury. | Compared to placebo treatment, NMN treatment of older adults with DKD will assess for improvements in biomarkers of kidney injury in association with DKD prognosis by measuring KIM-1 and STNFR1 combinedly. | 6 month | 
| Change from baseline in the levels of serum creatinine over 6-month intervention period | To determine whether NMN treatment is associated with change in serum creatinine from baseline to 24 weeks between the two study arms. | 6 month | 
| Change from baseline in the levels of cystine C over 6-month intervention period. | To determine whether NMN treatment is associated with change in cystatin C from baseline to 24 weeks between the two study arms. | 6 month | 
| To determine whether NMN treatment is associated with significantly greater improvement in muscle endurance. | Assess the change from baseline in muscle endurance by exercises (reps to failure) using Keiser Machines | 6 month | 
| Assess the change from baseline in performance-based measures of function. | To determine whether NMN treatment is associated with significantly greater improvement in performance based by using 6-minute walking distance measure of function. | 6 month | 
| To determine whether NMN alters the circulating biomarkers of aging that the geroscience experts have recommended. | Compared to placebo treatment, NMN treatment will be assessed to identify greater changes in the circulating biomarkers of aging. the biomarkers that will be assessed are IL6 and TNFalpha | 6 months | 
| Assess the change from baseline in the levels of NMN in the peripheral blood and in the PBMCs using a validated LC-MS/MS assay. | NMN treatment will be assessed to determine significant increases in blood levels of NAD and its metabolome during the 24-week intervention period. The increase in NAD levels are to be observed during the intervention period in NMN-treated subjects that will be sustained during the 12-week follow-up period (legacy effect). | 6 months | 
| Assess the change in measure of H1bac as a measure of glycemic control over the 6 months intervention period. | To determine the effect of NMN treatment on Hb1ac (expressed in mg/dL) in the body as a measure of glycemic control. | 6 months | 
| Assess the change in measure of fasting glucose as a measure of glycemic control over the 6 months intervention period. | To determine the effect of NMN treatment on fasting glucose in the body as a measure of glycemic control. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diabetes, type 2 diabetes, kidney disease