NAD Augmentation to Prevent or Reverse Alzheimer's Disease in People With Down Syndrome

NCT07278492 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 2025p002197
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

Brief Summary

The aim of the study is to determine the safety and tolerability of different increasing doses of MIB-626 (a microcrystalline form of β nicotinamide mononucleotide; NMN) given daily for 28 consecutive days to adults with Down syndrome (DS). The study will also explore how the drug moves through the body over time (pharmacokinetics or PK) and how the drug affects the body in different ways (pharmacodynamics or PD). The study participants will be monitored for adverse events and measurements to detect safety events will take place including laboratory tests of blood counts, chemistries and coagulation profile, and electrocardiogram (ECG). The trial will enroll a total of 24 adults with DS who are 18 years or older and are medically stable. People enrolled in the study will be randomly assigned to receive either the active intervention (MIB-626) tablets, or placebo tablets for 28 days. Study participants will be followed for an additional 28 days (total 56 days of follow-up). This study will also explore the effect of MIB-626 on different measures associated with aging and risk of Alzheimer's Disease (AD).

Conditions

Down Syndrome (DS)

Keywords

Down Syndrome; NMN; safety

Outcome Measures

Primary Outcomes (2)

• Treatment emergent adverse events

  All treatment emergent adverse events

  Baseline to 56 days after drug administration

• Treatment emergent serious adverse events

  All treatment emergent serious adverse events

  Baseline to 56 days after drug administration

Secondary Outcomes (13)

• Pharmacokinetics of NMN

  Baseline to 56 days

• Pharmacodynamics - steady state concentration of NAD+ in the brain

  Baseline and Day 28

• Pharmacodynamics - Blood NAD+ level

  Baseline to Day 56

• Pharmacodynamics - Plasma concentrations of NAD+ metabolites

  Pre-dose up to Day 28

• Urine concentration of NAD+

  Day 1 and Day 28

Other Outcomes (2)

• Muscle strength and endurance

  Baseline to Day 28

• Physical Function

  Baseline to Day 28

Study Arms (2)

Safety and pharmacokinetic ascending dose intervention group

EXPERIMENTAL

MIB-626 tablets will be provided at dose strength of 500mg. Three doses will be studied in ascending order: 500 mg (one tablet) once daily; 1000 mg (two 500 mg tablets once daily) or 1000 mg (two 500 mg tablets) twice daily.

Drug: MIB-626

Placebo tablets

PLACEBO COMPARATOR

Matching placebo tablets (number and frequency of tablets will match the active intervention group at each of the three doses)

Drug: Placebo

Interventions

MIB-626 DRUG

MIB-626 tablets will be provided at dose strength of 500mg. Three doses will be studied in ascending order: 500 mg (one tablet) once daily; 1000 mg (two 500 mg tablets once daily) or 1000 mg (two 500 mg tablets) twice daily.

Safety and pharmacokinetic ascending dose intervention group

Placebo DRUG

Matching placebo tablets (number and frequency of tablets will match the active intervention group at each of the three doses)

Placebo tablets

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A diagnosis of full trisomy for chromosome 21 or complete unbalanced translocation of chromosome 21, confirmed by karyotype analysis or clinical documentation.
• years or older
• Participant has a caregiver/ informant who has direct contact with the participant \>10 hours/ week and who can provide information about participant's health
• Participant or Legal Authorized Representative is able to understand and willing to provide written informed consent and capable of completing study assessments.
• In addition, female participants must Not be pregnant and not planning to become pregnant over the next 6 months.

You may not qualify if:

• Fasting morning UACR \> 5,000 mg/ g creatinine
• Other laboratory abnormalities:
• Has AST or ALT \> 3 times the upper limit of normal
• eGFR \< 30 mL/ min / 1.73 m2
• 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
• Current alcohol or substance use disorder or dependence (DSM 5 criteria).
• Major depressive disorder, bipolar disorder, schizophrenia, or current psychotic symptoms or behavioral problems that could interfere with study procedures.
• An acute illness, including COVID-19, requiring hospitalization within the past 3 months or any acute illness, including COVID-19, within the past month.
• Has a history of anaphylaxis from vitamin B3 derivatives
• BMI \> 42.5 kg/ m2
• Non-ambulatory

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• National Institutes of Health (NIH): collaborator

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Down Syndrome

Condition Hierarchy (Ancestors)

Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn

Study Officials

• Shalender K Bhasin, MB, BS

  Brigham and Women's Hosptial

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nancy Latham, PhD

CONTACT

6179999195; nklatham@bwh.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: This is a randomized, double-blind, placebo controlled multiple ascending dose trial of NMN in adults with DS.

Study Record Dates

• First Submitted: November 24, 2025
• First Posted: December 12, 2025
• Study Start: April 1, 2026
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): June 30, 2028
• Last Updated: December 12, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)