DKD: NAD Augmentation in Diabetes Kidney Disease
Study Details
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 |
|---|---|---|
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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
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 Names:
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| 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:
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Outcome Measures
Primary Outcome Measures
- The primary endpoint is the change from baseline in UACR over the 6-month intervention period. [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
- Assess the proportion of participants in the two study arms with 30% or greater reduction in UACR [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
- Assess the change from baseline over the 6-month intervention period in biomarkers of kidney injury. [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.
- Change from baseline in the levels of serum creatinine over 6-month intervention period [6 month]
To determine whether NMN treatment is associated with change in serum creatinine from baseline to 24 weeks between the two study arms.
- Change from baseline in the levels of cystine C over 6-month intervention period. [6 month]
To determine whether NMN treatment is associated with change in cystatin C from baseline to 24 weeks between the two study arms.
- To determine whether NMN treatment is associated with significantly greater improvement in muscle endurance. [6 month]
Assess the change from baseline in muscle endurance by exercises (reps to failure) using Keiser Machines
- Assess the change from baseline in performance-based measures of function. [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.
- To determine whether NMN alters the circulating biomarkers of aging that the geroscience experts have recommended. [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
- 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. [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).
- Assess the change in measure of H1bac as a measure of glycemic control over the 6 months intervention period. [6 months]
To determine the effect of NMN treatment on Hb1ac (expressed in mg/dL) in the body as a measure of glycemic control.
- Assess the change in measure of fasting glucose as a measure of glycemic control over the 6 months intervention period. [6 months]
To determine the effect of NMN treatment on fasting glucose in the body as a measure of glycemic control.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Has T2DM, as indicated by any of the following:
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Self-report of diabetes plus the use of a prescribed diabetes medication.
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ICD-10 code for diabetes plus current use of a diabetes medication in the electronic medical record.
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HbA1c >6.4%; or 2 fasting glucose > 125 mg/dL
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Fasting morning UACR between 100 and 2,000 mg/g creatinine on two separate days
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If UACR is > 300 mg/g creatinine, must be currently using an ACE inhibitor or an ARB
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eGFR > 30 mL/ min / 1.73 m2
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Hemoglobin A1c <9%
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Able to speak English or Spanish
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Willing and able to provide written informed consent
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In addition, female participants must Not be pregnant and not planning to become pregnant over the next 6 months
Exclusion Criteria:
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Fasting morning UACR > 2,000 mg/ g creatinine
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Other laboratory abnormalities:
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Has AST or ALT > 3 times the upper limit of normal
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creatinine > 2.5 mg/dL
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Hematocrit < 0.34 or 0.50 L/L
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A major adverse cardiovascular event in preceding 3 months
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Participation in an investigational trial to evaluate pharmaceuticals or biologics within the past 3 months or 5 half-lives, whichever is shorter
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Hypoglycemia unawareness or other medical conditions which could jeopardize participant's safety.
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History of alcohol or substance use disorder or dependence (DSM 5 criteria) within the last 2 years.
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Major depressive disorder, bipolar disorder, schizophrenia, or current psychotic symptoms or behavioral problems that could interfere with study procedures.
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BMI > 42.5 kg/ m2
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Brigham and Women's Hospital
- Boston Medical Center
Investigators
- Principal Investigator: Shalender Bhasin, MD, Brigham and Women's Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2021P003702