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

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).

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.

• Placebo · DRUG

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

Published eligibility criteria

Verbatim from the registry. Only the site can decide how these apply to a specific patient.

Inclusion Criteria:

1. A diagnosis of full trisomy for chromosome 21 or complete unbalanced translocation of chromosome 21, confirmed by karyotype analysis or clinical documentation.
2. 18 years or older
3. Participant has a caregiver/ informant who has direct contact with the participant \>10 hours/ week and who can provide information about participant's health
4. Participant or Legal Authorized Representative is able to understand and willing to provide written informed consent and capable of completing study assessments.
5. 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 \< 30 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. Non-ambulatory

Sites (2)

• Massachusetts General Hospital, Boston, Massachusetts
• Brigham and Women's Hospital, Boston, Massachusetts