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Trial record 3 of 4 for:    vitamin b3 | Alzheimer Disease

Effects of Nicotinamide Riboside on Bioenergetics and Oxidative Stress in Mild Cognitive Impairment/Alzheimer's Dementia

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ClinicalTrials.gov Identifier: NCT04430517
Recruitment Status : Recruiting
First Posted : June 12, 2020
Last Update Posted : April 5, 2021
Sponsor:
Collaborator:
National Institute on Aging (NIA)
Information provided by (Responsible Party):
Fei Du, Mclean Hospital

Tracking Information
First Submitted Date  ICMJE May 29, 2020
First Posted Date  ICMJE June 12, 2020
Last Update Posted Date April 5, 2021
Estimated Study Start Date  ICMJE April 7, 2021
Estimated Primary Completion Date April 30, 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 11, 2020)
  • Changes in brain NAD+ [ Time Frame: Baseline, 6 and 12 weeks, pre- and post- 1000 mg NR daily ]
    Changes in brain NAD+ levels
  • Changes in brain redox state [ Time Frame: Baseline, 6 and 12 weeks, pre- and post- 1000 mg NR daily ]
    Changes in brain NAD+/NADH ratio
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 11, 2020)
  • Changes in mitochondrial function [ Time Frame: Baseline, 6 and 12 weeks, pre- and post- 1000 mg NR daily ]
    Changes in brain CK/ATPase activity
  • Changes in antioxidant glutathione (GSH) levels [ Time Frame: Baseline, 6 and 12 weeks, pre- and post- 1000 mg NR daily ]
    Changes in brain GSH levels
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: June 11, 2020)
  • Changes in cognitive status [ Time Frame: Baseline, 6 and 12 weeks, pre- and post- 1000 mg NR daily ]
    Changes in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) scores. The RBANS provides a total score from 40-160, with a higher score indicating a better outcome.
  • Changes in functional status [ Time Frame: Baseline, 6 and 12 weeks, pre- and post- 1000 mg NR daily ]
    Changes in Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scores. The ADCS-ADL provides a total score from 0-78, with a higher score indicating lower severity and a better outcome.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Effects of Nicotinamide Riboside on Bioenergetics and Oxidative Stress in Mild Cognitive Impairment/Alzheimer's Dementia
Official Title  ICMJE Effects of Orally Administered Nicotinamide Riboside on Bioenergetic Metabolism, Oxidative Stress and Cognition in Mild Cognitive Impairment and Mild Alzheimer's Dementia
Brief Summary The primary aim of this study is to investigate the effects of exogenously administered nicotinamide riboside (NR) on brain energy metabolism, oxidative stress, and cognitive function in individuals with mild cognitive impairment (MCI) and mild Alzheimer's dementia (AD).
Detailed Description Mitochondrial function is mediated, in part, by nicotinamide adenine dinucleotide (NAD). Unfortunately, decreases in NAD+ levels are associated with normal aging, and also with numerous diseases such as AD. Accumulating evidence suggests that NR can enhance mitochondrial function and help slow or reverse these age-related abnormalities. Numerous preclinical and clinical studies have been performed using NR and related compounds to boost NAD+ level in human subjects with various diseases or animal models. However, no studies to date have investigated in vivo metabolic and bioenergetic changes (target engagement) associated with NR supplementation. In this project, we aim to investigate the neurobiological mechanisms and clinical effects of NR in patients with MCI and mild AD using in vivo novel neuroimaging techniques.
Study Type  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE
  • Mild Cognitive Impairment
  • Alzheimer Disease
Intervention  ICMJE Drug: Nicotinamide riboside
Participants will take 4 pills every day, each containing 250 mg NR (NIAGEN® by Chromadex; www.chromadex.com), via the oral route, for 12 weeks.
Other Name: Chromadex NIAGEN
Study Arms  ICMJE Experimental: Mild Cognitive Impairment and Alzheimer's Dementia
Participants will take 4 pills every day, each containing 250 mg NR (NIAGEN® by Chromadex; www.chromadex.com), via the oral route, for 12 weeks.
Intervention: Drug: Nicotinamide riboside
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 11, 2020)
50
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 30, 2025
Estimated Primary Completion Date April 30, 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Ability of the participant and/or his/her legally authorized representative to understand the purpose and risks of the study, to provide signed and dated informed consent, and to authorize the use of confidential health information.
  • Ability to speak and read fluently in English
  • 55-89 years old (inclusive)
  • Normal or corrected to normal hearing and vision
  • Meet clinical diagnostic criteria for MCI or Mild AD, according to the following criteria:

    1. CDR Global Score of 0.5 (MCI) or 1.0 (mild AD)
    2. MoCA total score of 19-25 (MCI) or 11-21 (mild AD)
    3. 2018 NIA-AA guidelines for MCI/mild AD
  • Study partner available for the duration of trial participation
  • At least one copy of the APOE ε4 allele
  • An aggregate risk score > 4 according to the risk analysis method developed by Sabbagh et al. (2017)
  • For individuals who are taking niacin (or a vitamin supplement with niacin) of >200mg, the completion of a two-week wash-out period

Exclusion Criteria:

  • Current serious or unstable medical or neurological condition that could affect cognitive functioning, as determined by study clinician
  • Clinically unstable mood or anxiety disorder within 6 months prior to screening, as determined by study clinician
  • Lifetime history of psychotic disorder (i.e. Schizophrenia, Schizoaffective Disorder), as determined by study clinician
  • Diagnosis of a mitochondrial disorder
  • Any MRI safety contraindications
  • History of drug hypersensitivity or intolerance to NR
  • Transient ischemic attack or stroke within 1 year prior to screening
  • History of alcohol or substance abuse within prior year, as determined by study clinician and urine toxicology screen
  • History of head injury rated as moderate or worse, per DSM-5 criteria
  • History of seizure within prior 10 years
  • Current use of medication with known adverse effects on cognition (benzodiazepines, barbiturates, opiate analgesics, first generation antipsychotic medication, anticholinergics, sedating antihistamines, tricyclic anti-depressants)
  • Change in dose of any psychiatric medications within 4 weeks of screening visit
  • Prior use of L-DOPA, any anti-Parkinsonian medication, or prior treatment with anti-amyloid immunotherapy
  • Current use of putative mitochondrial enhancers and antioxidants (e.g Vitamin E, carnitine, creatine Co-Q10, pramipexole, N-acetyl cysteine [NAC])
  • Initiation of treatment or change in dosing of acetylcholinesterase inhibitors (AChEIs) and memantine within 4 weeks of screening
  • Prior use of prescription narcotics 4 weeks before screening
  • Female subjects who are pregnant or breastfeeding
  • The use of current use of niacin (or a vitamin supplement with niacin) >200mg within the last two weeks prior to study visit.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 55 Years to 89 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Fei Du, PhD 6178552710 fdu@mclean.harvard.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04430517
Other Study ID Numbers  ICMJE 2020P001652
1R01AG066670 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: The proposed research will include data and biosamples from 50 subjects who will receive open-label treatment with nicotinamide riboside (NR) throughout the duration of the 12-week study. At the time of publication of the primary results or within 9 months of database lock, whichever comes first, we will create deidentified datasets, which could be available for research purposes to qualified individuals within the scientific community.
Supporting Materials: Study Protocol
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: At the time of publication of the primary results or within 9 months of database lock, whichever comes first, we will create deidentified datasets, which could be available for research purposes to qualified individuals within the scientific community.
Access Criteria: Data are available to users only under a data-sharing agreement. All users will provide to PIs a proposal of hypotheses, variables needed to test these hypotheses, and plans for dissemination of findings. All users will indicate in a signed document: (1) a commitment to using the data only for research purposes and not to identify any participant, clinician, or plan; (2) a plan for securing the data using appropriate technology/data use protocols; (3) an agreement to either destroy or return the data once analyses are completed or by a specific negotiated date; (4) appropriate IRB approval; (5) a commitment that the information provided to users will not be used for commercial purposes, will not be redistributed to third parties, or shared with any others not on the research team; (6) adequate funding/resources to analyze the data and publish results. All findings generated will be described via peer-reviewed articles in scientific journals made available via PubMed Central.
Responsible Party Fei Du, Mclean Hospital
Study Sponsor  ICMJE Mclean Hospital
Collaborators  ICMJE National Institute on Aging (NIA)
Investigators  ICMJE
Principal Investigator: Fei Du, PhD Mclean Hospital
Principal Investigator: Brent Forester, MD, MSc Mclean Hospital
PRS Account Mclean Hospital
Verification Date April 2021

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