NAD Augmentation in Diabetes Kidney Disease (DKD)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Diabetic Kidney Disease; Type2diabetes
• Intervention / Treatment: Drug: Investigational Product - MIB 626; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 156
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Shalender Bhasin, MD; Phone Number: 6175259150; Email: sbhasin@bwh.harvard.edu
• Study Contact Backup: Name: Nancy Latham, PhD; Phone Number: 6179999195; Email: nklatham@bwh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Brigham and Women's Hospital
      • Principal Investigator: Shalender Bhasin, MB BS
      • Sub-Investigator: Nancy Latham, PhD
      • Contact: Nancy K Latham, PhD; Phone Number: 6179999195; Email: nklatham@bwh.harvard.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. A man or a postmenopausal woman (complete cessation of menses for one or more years and /or FSH > 20 U/L), 30 years or older

2. Has type 1 or type 2 diabetes mellitus, as indicated by any of the following:

   1. Self-report of type 1 or type 2 diabetes plus the use of a prescribed medication.
   2. ICD-10 code for type 1 or type 2 diabetes plus current use of a medication in the electronic medical record.
   3. HbA1c >6.4%; or 2 fasting glucose > 125 mg/dL

3. Has an average of two or more morning UACR equal to or above 100mg/g creatinine each of which must be equal to or greater than 60 mg / g creatinine with at least one UACR value measured during the screening visit.

   a. Recent UACR value in the medical record within the preceding 3 months prior to screening is acceptable.

4. If type 2 diabetic and UACR is > 300 mg/g creatinine, must be currently using an ACE inhibitor or an ARB or a SGLT2 inhibitor.
5. eGFR > 25 mL/ min / 1.73 m2
6. Hemoglobin A1c <10%
7. Able to speak English or Spanish or Haitian Creole
8. Willing and able to provide written informed consent
9. In addition, female participants must Not be pregnant and not planning to become pregnant over the next 6 months.

Exclusion criteria:

1. Fasting morning UACR > 5,000 mg/ g creatinine

2. Other laboratory abnormalities:

   1. Has AST or ALT > 3 times the upper limit of normal
   2. eGFR < 25 mL/ min / 1.73 m2
   3. Hematocrit < 0.34 or > 0.50 L/L
3. A major adverse cardiovascular event in preceding 3 months
4. Participation in an investigational trial to evaluate pharmaceuticals or biologics within the past 3 months or 5 half-lives, whichever is shorter
5. Current alcohol or substance use disorder or dependence (DSM 5 criteria).
6. Major depressive disorder, bipolar disorder, schizophrenia, or current psychotic symptoms or behavioral problems that could interfere with study procedures.
7. An acute illness, including COVID-19, requiring hospitalization within the past 3 months or any acute illness, including COVID-19, within the past month.
8. Has a history of anaphylaxis from vitamin B3 derivatives
9. BMI > 42.5 kg/ m2
10. If patient has a confirmed diagnosis of type 3 diabetes, or gestational diabetes.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Investigational Product - MIB 626; 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; 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.; Other Names: NMN
Placebo Comparator: Placebo; Participants randomized to placebo will receive Matching placebo tablets will be provided by Metro International Biotech, LLC.	Drug: Placebo; Placebo - Participants randomized to placebo will receive Matching placebo tablets will be provided by Metro International Biotech, LLC.; Other Names: Placebo for NMN

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Collaborators: Boston Medical Center
• Investigators: Principal Investigator: Shalender Bhasin, MD, Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 13, 2023
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): March 31, 2027

Study Registration Dates

• First Submitted: January 9, 2023
• First Submitted That Met QC Criteria: March 6, 2023
• First Posted (Actual): March 8, 2023

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 8, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: diabetes; kidney disease; type 2 diabetes
• Additional Relevant MeSH Terms: Urogenital Diseases; Endocrine System Diseases; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Complications; Nutritional and Metabolic Diseases; Diabetes Mellitus, Type 2; Diabetes Mellitus; Kidney Diseases; Diabetic Nephropathies; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs
• Other Study ID Numbers: 2021P003702

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be shared

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No