NAD Augmentation in Diabetes Kidney Disease

Diabetic Kidney Disease Clinical Trial

— DKD  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05759468
• Other study ID #: 2021P003702
• Status: Recruiting
• Phase: Phase 2
• Start date: April 13, 2023
• Est. completion date: July 1, 2026

Study information

• Verified date: April 2023
• Source: Brigham and Women's Hospital
• Contact: Shalender Bhasin, MD
• Phone: 6175259150
• Email: sbhasin[@]bwh.harvard.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 140
• Est. completion date: July 1, 2026
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Diabetic Kidney Disease
• Diabetic Nephropathies
• Kidney Diseases

Intervention

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

Locations

Country	Name	City	State
United States	Brigham and Women's Hospital	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Brigham and Women's Hospital	Boston Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 ß nicotinamide mononucleotide (ßNMN) in older adults with DKD improves urinary albumin to creatinine excretion ratio (UACR), compared to placebo.	6 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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