NAD Augmentation in Diabetes Kidney Disease (DKD)

• ClinicalTrials.gov Identifier: NCT05759468
• Recruitment Status: Recruiting
• First Posted: March 8, 2023
• Last Update Posted: April 25, 2023
• Sponsor: Brigham and Women's Hospital
• Collaborator: Boston Medical Center
• Information provided by (Responsible Party): Shalendar Bhasin, MD, Brigham and Women's Hospital

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Type2diabetes; Diabetic Kidney Disease	Drug: Investigational Product - MIB 626; Drug: Placebo	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 140 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention 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 (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description

The study is double-blind in that the study participants and the study staff involved in outcomes assessments will be unaware of the intervention assignment. The randomization schedule will be masked from all study personnel except those specifically designated below.

1. The unblinded study biostatistician
2. The staff of the Investigational Drug Pharmacy Services.
3. The DSMB, if requested

• Primary Purpose: Treatment
• Official Title: NAD Augmentation to Treat Diabetes Kidney Disease: A Randomized Controlled Trial
• Actual Study Start Date: April 13, 2023
• Estimated Primary Completion Date: December 31, 2025
• Estimated Study Completion Date: July 1, 2026

Arms and Interventions

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 Name: 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 Name: Placebo for NMN

Outcome Measures

Primary Outcome Measures :

1. The primary endpoint is the change from baseline in UACR over the 6-month intervention period. [ Time Frame: 6 months ]
   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.

Secondary Outcome Measures :

1. Assess the proportion of participants in the two study arms with 30% or greater reduction in UACR [ Time Frame: 6 months ]
   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
2. Assess the change from baseline over the 6-month intervention period in biomarkers of kidney injury. [ Time Frame: 6 month ]
   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.
3. Change from baseline in the levels of serum creatinine over 6-month intervention period [ Time Frame: 6 month ]
   To determine whether NMN treatment is associated with change in serum creatinine from baseline to 24 weeks between the two study arms.
4. Change from baseline in the levels of cystine C over 6-month intervention period. [ Time Frame: 6 month ]
   To determine whether NMN treatment is associated with change in cystatin C from baseline to 24 weeks between the two study arms.
5. To determine whether NMN treatment is associated with significantly greater improvement in muscle endurance. [ Time Frame: 6 month ]
   Assess the change from baseline in muscle endurance by exercises (reps to failure) using Keiser Machines
6. Assess the change from baseline in performance-based measures of function. [ Time Frame: 6 month ]
   To determine whether NMN treatment is associated with significantly greater improvement in performance based by using 6-minute walking distance measure of function.
7. To determine whether NMN alters the circulating biomarkers of aging that the geroscience experts have recommended. [ Time Frame: 6 months ]
   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
8. 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. [ Time Frame: 6 months ]
   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).
9. Assess the change in measure of H1bac as a measure of glycemic control over the 6 months intervention period. [ Time Frame: 6 months ]
   To determine the effect of NMN treatment on Hb1ac (expressed in mg/dL) in the body as a measure of glycemic control.
10. Assess the change in measure of fasting glucose as a measure of glycemic control over the 6 months intervention period. [ Time Frame: 6 months ]
    To determine the effect of NMN treatment on fasting glucose in the body as a measure of glycemic control.

Eligibility Criteria

• Ages Eligible for Study: 60 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Has T2DM, as indicated by any of the following:

   1. Self-report of diabetes plus the use of a prescribed diabetes medication.
   2. ICD-10 code for diabetes plus current use of a diabetes medication in the electronic medical record.
   3. HbA1c >6.4%; or 2 fasting glucose > 125 mg/dL
2. Fasting morning UACR between 100 and 2,000 mg/g creatinine on two separate days
3. If UACR is > 300 mg/g creatinine, must be currently using an ACE inhibitor or an ARB
4. eGFR > 30 mL/ min / 1.73 m2
5. Hemoglobin A1c <9%
6. Able to speak English or Spanish
7. Willing and able to provide written informed consent
8. 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 > 2,000 mg/ g creatinine

2. Other laboratory abnormalities:

   1. Has AST or ALT > 3 times the upper limit of normal
   2. creatinine > 2.5 mg/dL
   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. Hypoglycemia unawareness or other medical conditions which could jeopardize participant's safety.
6. History of alcohol or substance use disorder or dependence (DSM 5 criteria) within the last 2 years.
7. Major depressive disorder, bipolar disorder, schizophrenia, or current psychotic symptoms or behavioral problems that could interfere with study procedures.
8. BMI > 42.5 kg/ m2

Contacts and Locations

Contacts

Contact: Shalender Bhasin, MD; 6175259150; sbhasin@bwh.harvard.edu

Contact: Nancy Latham, PhD; 6179999195; nklatham@bwh.harvard.edu

Locations

United States, Massachusetts

Brigham and Women's Hospital; Recruiting

Boston, Massachusetts, United States, 02115

Contact: Nancy K Latham, PhD 617-999-9195 nklatham@bwh.harvard.edu

Principal Investigator: Shalender Bhasin, MB BS

Sub-Investigator: Nancy Latham, PhD

Sponsors and Collaborators

Brigham and Women's Hospital

Boston Medical Center

Investigators

• Principal Investigator: Shalender Bhasin, MD; Brigham and Women's Hospital

More Information

• Responsible Party: Shalendar Bhasin, MD, Principal Investigator, Professor of Medicine, Harvard Medical School Director, Research Program in Men's Health: Aging and Metabolism Co-Director, BWH Center for Transgender Health Director, Boston Claude D. Pepper Older Americans Independence Center, Brigham and Women's Hospital
• ClinicalTrials.gov Identifier: NCT05759468
• Other Study ID Numbers: 2021P003702
• First Posted: March 8, 2023
• Last Update Posted: April 25, 2023
• Last Verified: April 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: Individual participant data will not be shared

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Shalendar Bhasin, MD, Brigham and Women's Hospital:

diabetes; type 2 diabetes; kidney disease

Additional relevant MeSH terms:

Kidney Diseases; Diabetic Nephropathies; Diabetes Mellitus; Diabetes Mellitus, Type 2; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Diabetes Complications