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NAD Augmentation in Diabetes Kidney Disease (DKD)

Primary Purpose

Type2diabetes, Diabetic Kidney Disease

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Investigational Product - MIB 626
Placebo
Sponsored by
Brigham and Women's Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Type2diabetes focused on measuring diabetes, type 2 diabetes, kidney disease

Eligibility Criteria

60 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Has T2DM, as indicated by any of the following: Self-report of diabetes plus the use of a prescribed diabetes medication. ICD-10 code for diabetes plus current use of a diabetes medication in the electronic medical record. HbA1c >6.4%; or 2 fasting glucose > 125 mg/dL Fasting morning UACR between 100 and 2,000 mg/g creatinine on two separate days If UACR is > 300 mg/g creatinine, must be currently using an ACE inhibitor or an ARB eGFR > 30 mL/ min / 1.73 m2 Hemoglobin A1c <9% Able to speak English or Spanish 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 > 2,000 mg/ g creatinine Other laboratory abnormalities: Has AST or ALT > 3 times the upper limit of normal creatinine > 2.5 mg/dL 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 Hypoglycemia unawareness or other medical conditions which could jeopardize participant's safety. History of alcohol or substance use disorder or dependence (DSM 5 criteria) within the last 2 years. Major depressive disorder, bipolar disorder, schizophrenia, or current psychotic symptoms or behavioral problems that could interfere with study procedures. BMI > 42.5 kg/ m2

Sites / Locations

  • Brigham and Women's HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Investigational Product - MIB 626

Placebo

Arm Description

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.

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

Outcomes

Primary Outcome Measures

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 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
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.
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
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.
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.
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.
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.
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.
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.
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.
To determine the effect of NMN treatment on fasting glucose in the body as a measure of glycemic control.

Full Information

First Posted
January 9, 2023
Last Updated
April 21, 2023
Sponsor
Brigham and Women's Hospital
Collaborators
Boston Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT05759468
Brief Title
NAD Augmentation in Diabetes Kidney Disease
Acronym
DKD
Official Title
NAD Augmentation to Treat Diabetes Kidney Disease: A Randomized Controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 13, 2023 (Actual)
Primary Completion Date
December 31, 2025 (Anticipated)
Study Completion Date
July 1, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Brigham and Women's Hospital
Collaborators
Boston Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type2diabetes, Diabetic Kidney Disease
Keywords
diabetes, type 2 diabetes, kidney disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
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.
Masking
ParticipantCare ProviderInvestigatorOutcomes 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. The unblinded study biostatistician The staff of the Investigational Drug Pharmacy Services. The DSMB, if requested
Allocation
Randomized
Enrollment
140 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Investigational Product - MIB 626
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants randomized to placebo will receive Matching placebo tablets will be provided by Metro International Biotech, LLC.
Intervention Type
Drug
Intervention Name(s)
Investigational Product - MIB 626
Other Intervention Name(s)
NMN
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Placebo for NMN
Intervention Description
Placebo - Participants randomized to placebo will receive Matching placebo tablets will be provided by Metro International Biotech, LLC.
Primary Outcome Measure Information:
Title
The primary endpoint is the change from baseline in UACR over the 6-month intervention period.
Description
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.
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Assess the proportion of participants in the two study arms with 30% or greater reduction in UACR
Description
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
Time Frame
6 months
Title
Assess the change from baseline over the 6-month intervention period in biomarkers of kidney injury.
Description
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.
Time Frame
6 month
Title
Change from baseline in the levels of serum creatinine over 6-month intervention period
Description
To determine whether NMN treatment is associated with change in serum creatinine from baseline to 24 weeks between the two study arms.
Time Frame
6 month
Title
Change from baseline in the levels of cystine C over 6-month intervention period.
Description
To determine whether NMN treatment is associated with change in cystatin C from baseline to 24 weeks between the two study arms.
Time Frame
6 month
Title
To determine whether NMN treatment is associated with significantly greater improvement in muscle endurance.
Description
Assess the change from baseline in muscle endurance by exercises (reps to failure) using Keiser Machines
Time Frame
6 month
Title
Assess the change from baseline in performance-based measures of function.
Description
To determine whether NMN treatment is associated with significantly greater improvement in performance based by using 6-minute walking distance measure of function.
Time Frame
6 month
Title
To determine whether NMN alters the circulating biomarkers of aging that the geroscience experts have recommended.
Description
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
Time Frame
6 months
Title
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.
Description
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).
Time Frame
6 months
Title
Assess the change in measure of H1bac as a measure of glycemic control over the 6 months intervention period.
Description
To determine the effect of NMN treatment on Hb1ac (expressed in mg/dL) in the body as a measure of glycemic control.
Time Frame
6 months
Title
Assess the change in measure of fasting glucose as a measure of glycemic control over the 6 months intervention period.
Description
To determine the effect of NMN treatment on fasting glucose in the body as a measure of glycemic control.
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Has T2DM, as indicated by any of the following: Self-report of diabetes plus the use of a prescribed diabetes medication. ICD-10 code for diabetes plus current use of a diabetes medication in the electronic medical record. HbA1c >6.4%; or 2 fasting glucose > 125 mg/dL Fasting morning UACR between 100 and 2,000 mg/g creatinine on two separate days If UACR is > 300 mg/g creatinine, must be currently using an ACE inhibitor or an ARB eGFR > 30 mL/ min / 1.73 m2 Hemoglobin A1c <9% Able to speak English or Spanish 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 > 2,000 mg/ g creatinine Other laboratory abnormalities: Has AST or ALT > 3 times the upper limit of normal creatinine > 2.5 mg/dL 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 Hypoglycemia unawareness or other medical conditions which could jeopardize participant's safety. History of alcohol or substance use disorder or dependence (DSM 5 criteria) within the last 2 years. Major depressive disorder, bipolar disorder, schizophrenia, or current psychotic symptoms or behavioral problems that could interfere with study procedures. BMI > 42.5 kg/ m2
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Shalender Bhasin, MD
Phone
6175259150
Email
sbhasin@bwh.harvard.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Nancy Latham, PhD
Phone
6179999195
Email
nklatham@bwh.harvard.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shalender Bhasin, MD
Organizational Affiliation
Brigham and Women's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nancy K Latham, PhD
Phone
617-999-9195
Email
nklatham@bwh.harvard.edu
First Name & Middle Initial & Last Name & Degree
Shalender Bhasin, MB BS
First Name & Middle Initial & Last Name & Degree
Nancy Latham, PhD

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
Individual participant data will not be shared

Learn more about this trial

NAD Augmentation in Diabetes Kidney Disease

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