Diabetic Kidney Disease, Type2diabetes
Conditions
Keywords
diabetes, type 2 diabetes, kidney disease
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.
Interventions
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.
DRUGPlacebo
Placebo - Participants randomized to placebo will receive Matching placebo tablets will be provided by Metro International Biotech, LLC.
Sponsors
Brigham and Women's Hospital
Boston Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, 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
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.
Eligibility
Sex/Gender
ALL
Age
30 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Contacts
CONTACTShalender Bhasin, MD
CONTACTNancy Latham, PhD
PRINCIPAL_INVESTIGATORShalender Bhasin, MD
Brigham and Women's Hospital
Outcome results
None listed