NAD Augmentation in Diabetes Kidney Disease

Purpose

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.

Conditions

  • Type2diabetes
  • Diabetic Kidney Disease

Eligibility

Eligible Ages
Over 30 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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 Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
This will be three 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.
Primary Purpose
Treatment
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

Arm Groups

ArmDescriptionAssigned Intervention
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

Recruiting Locations

Brigham and Women's Hospital
Boston, Massachusetts 02115
Contact:
Nancy K Latham, PhD
6179999195
nklatham@bwh.harvard.edu

More Details

Status
Recruiting
Sponsor
Brigham and Women's Hospital

Study Contact

Shalender Bhasin, MD
6175259150
sbhasin@bwh.harvard.edu

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.