Clinical trial NCT05759468: NAD Augmentation in Diabetes Kidney Disease
Official title: NAD Augmentation to Treat Diabetes Kidney Disease: A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Type2diabetes
Diabetic Kidney Disease
Keywords: diabetes
type 2 diabetes
kidney disease
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
Collaborators: name: Boston Medical Center
First posted: 2023-03-08
Enrollment: 140
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: The primary endpoint is the change from baseline in UACR over the 6-month intervention period.
timeFrame: 6 months
Secondary outcomes:
measure: Assess the proportion of participants in the two study arms with 30% or greater reduction in UACR
timeFrame: 6 months
measure: Assess the change from baseline over the 6-month intervention period in biomarkers of kidney injury.
timeFrame: 6 month
measure: Change from baseline in the levels of serum creatinine over 6-month intervention period
timeFrame: 6 month
measure: Change from baseline in the levels of cystine C over 6-month intervention period.
timeFrame: 6 month
measure: To determine whether NMN treatment is associated with significantly greater improvement in muscle endurance.
timeFrame: 6 month
measure: Assess the change from baseline in performance-based measures of function.
timeFrame: 6 month
measure: To determine whether NMN alters the circulating biomarkers of aging that the geroscience experts have recommended.
timeFrame: 6 months
measure: 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.
timeFrame: 6 months
measure: Assess the change in measure of H1bac as a measure of glycemic control over the 6 months intervention period.
timeFrame: 6 months
measure: Assess the change in measure of fasting glucose as a measure of glycemic control over the 6 months intervention period.
timeFrame: 6 months
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: Shalender Bhasin, MD
role: PRINCIPAL_INVESTIGATOR
References: