NAD Augmentation in Diabetes Kidney Disease

Official title

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

Overview

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

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.

Interventions

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

Primary outcome measures

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

Secondary outcome measures (10)

• Assess the proportion of participants in the two study arms with 30% or greater reduction in UACR [Time frame: 6 months]
• Assess the change from baseline over the 6-month intervention period in biomarkers of kidney injury. [Time frame: 6 month]
• Change from baseline in the levels of serum creatinine over 6-month intervention period [Time frame: 6 month]
• 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 significantly greater improvement in muscle endurance. [Time frame: 6 month]
• Assess the change from baseline in performance-based measures of function. [Time frame: 6 month]
• To determine whether NMN alters the circulating biomarkers of aging that the geroscience experts have recommended. [Time frame: 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. [Time frame: 6 months]
• Assess the change in measure of H1bac as a measure of glycemic control over the 6 months intervention period. [Time frame: 6 months]
• Assess the change in measure of fasting glucose as a measure of glycemic control over the 6 months intervention period. [Time frame: 6 months]

Eligibility criteria

Inclusion criteria

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

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

• 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.
• eGFR > 25 mL/ min / 1.73 m2
• Hemoglobin A1c <10%
• Able to speak English or Spanish or Haitian Creole
• 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 > 5,000 mg/ g creatinine
• Other laboratory abnormalities:

• Has AST or ALT > 3 times the upper limit of normal
• eGFR < 25 mL/ min / 1.73 m2
• 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
• Current alcohol or substance use disorder or dependence (DSM 5 criteria).
• Major depressive disorder, bipolar disorder, schizophrenia, or current psychotic symptoms or behavioral problems that could interfere with study procedures.
• An acute illness, including COVID-19, requiring hospitalization within the past 3 months or any acute illness, including COVID-19, within the past month.
• Has a history of anaphylaxis from vitamin B3 derivatives
• BMI > 42.5 kg/ m2
• If patient has a confirmed diagnosis of type 3 diabetes, or gestational diabetes.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 1 center

• Brigham and Women's Hospital — Boston

Identifiers

NCT: NCT05759468 · 2021P003702

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗