The NADage Study: Nicotinamide Riboside Replenishment Therapy Against Functional Decline in Aging

NCT06208527 | Recruiting Phase 2 DMC

• 1 other identifier: 2023/680827
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 2

Brief Summary

This clinical study, designed as a double-blind, randomized, placebo-controlled trial, aims to investigate the potential of nicotinamide riboside (NR) to decelerate functional decline in the elderly frail population. In animal studies, NR, which is converted to nicotinamide adenine dinucleotide (NAD), has shown potential as a neuroprotective agent, with indications of protection against amyotrophic lateral sclerosis (ALS), Alzheimer's dementia, and Parkinson's disease. Furthermore, aging is commonly associated with decreased tissue NAD levels, a phenomenon linked to premature aging and a spectrum of age-related disorders, including cardiovascular diseases and cancers. Existing preclinical and clinical research highlights the promise of NAD replenishment through enhanced DNA repair, sirtuin activity, and improved mitochondrial function. The research center has conducted two phase II clinical trials on NR for Parkinson's disease (NAD-PARK and NR-SAFE), administering up to 3000 mg of NR daily. These trials have shown promising results, indicating NR's potential as a treatment that may alter the course of the disease and possibly as neuroprotective treatment in Parkinson's disease. The NAD age trial primarily aims to determine:

• The efficacy of NAD therapy in improving clinical symptoms of frailty, evaluated through standardized physical and cognitive function tests.
• The safety of administering 2000 mg NR daily in an elderly frail population. The study will include 100 individuals, classified as frail based on the Fried Frailty Phenotype. Participants will be randomly assigned to receive either 2000 mg of NR daily or a placebo. Over a 52-week period, participants will undergo:
• Clinical evaluations, including actigraphy and questionnaires.
• Cognitive assessments.
• Bio sampling.
• Magnetic resonance imaging (MRI).
• Positron emission tomography (FDG-PET) scanning. The outcomes of this study could potentially demonstrate that NR effectively reduces signs of frailty, offering considerable advantages to the individuals affected, their families, and society as a whole.

Conditions

Frailty; Frail Elderly Syndrome; Frailty Syndrome; Aging

Keywords

Frailty; Nicotinamide Riboside; NR; Nicotinamide adenine dinucleotide; NAD; Frail; Aging; Functional decline

Outcome Measures

Primary Outcomes (1)

• The between-group (NR vs. Placebo) difference in the change in gait speed.

  Gait speed is assessed by the 6-minute walk test (6MWT).

  52 weeks

Secondary Outcomes (4)

• Incidence of treatment-emergent adverse events (safety and tolerability).

  52 weeks

• Change in physical performance assessed by the Short Physical Performance Battery (SPPB).

  52 weeks

• Change in physical performance assessed by hand grip strength.

  52 weeks

• Change in cognitive function assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) test battery.

  52 weeks

Other Outcomes (29)

• Change in daily step count.

  52 weeks

• Change in overall activity level.

  52 weeks

• Change in speed of movements.

  52 weeks

Study Arms (2)

Placebo group

PLACEBO COMPARATOR

Placebo, no active ingredients. Administered in tablet form twice daily for the duration of the trial (1 year).

Other: Placebo

NR group

EXPERIMENTAL

Nicotinamide Riboside (NR) administered in doses of 1000 mg twice daily for the duration of the trial (1 year).

Dietary Supplement: Nicotinamide Riboside (NR)

Interventions

Nicotinamide Riboside (NR) DIETARY_SUPPLEMENT

A total of 2000 mg NR is administered daily for 1 year.

NR group

Placebo OTHER

Placebo tablet identical in taste, shape and appearance to NR tablets.

Placebo group

Eligibility Criteria

• Age: 75 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Participant must understand the nature of the study and be able to provide written, informed consent.
• Male or female aged ≥ 75 years at baseline.
• Fried Frailty Phenotype score ≥ 3 to identify frail individuals.
• Montreal Cognitive Assessment (MoCA) at screening adjusted to age, gender, and educational level, with a threshold set at the 10th percentile (z-score ≤ -1.28).

You may not qualify if:

• Inability to provide informed consent.
• Does not reside in a facility or institution.
• Advanced disability, end-stage disease, presence of severe chronic illness and/or life expectancy of less than a year.
• Inability to complete a 6-minute walk test (6MWT) and/or contraindications to the procedure (history of unstable angina or myocardial infarction within 30 days prior to the test).
• Diagnosis of active malignancy in the last 2 years at baseline (exceptions include non-metastatic skin conditions and non-metastatic and/or treated prostate cancer with stable prostate-specific antigen (PSA) levels in six months prior to baseline). Specific considerations may apply depending on the type of cancer.
• Significant neurological or psychiatric disorders, including but not limited to psychotic disorders, severe bipolar or unipolar depression, multiple sclerosis, uncontrolled seizure conditions, and neurodegenerative disorder.
• A history of cerebrovascular events, excluding transient ischemic attack (TIA) that occurs more than 3 months prior to baseline.
• Hospitalization or major surgery within 3 months prior to baseline.
• Significant changes in medications or treatment plans made less than one month prior to baseline, judged by the site investigator to interfere with the subject's participation in the study.
• Consumption of NAD precursor supplements (e.g., Nicotinamide riboside, nicotinamide mononucleotide or Vitamin B3), or related supplements within 6 months prior to baseline.
• Elective surgeries scheduled during the study duration.
• Concurrent participation in other clinical trials with interventions that could affect frailty measures.
• Any medical history, at the discretion of the investigator, might hinder compliance with study procedures or increase risk to the participant.

Sponsors & Collaborators

• Haukeland University Hospital: lead

Study Sites (2)

Haukeland University Hospital

Bergen, Vestland, 5021, Norway

NOT YET RECRUITING

Haukeland University Hospital

Bergen, 5021, Norway

RECRUITING

MeSH Terms

Conditions

Frailty

Interventions

nicotinamide-beta-riboside

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Charalampos Tzoulis, PhD

  Haukeland University Hospital

  STUDY DIRECTOR

Central Study Contacts

Charalampos Tzoulis, PhD

CONTACT

55975061; charalampos.tzoulis@helse-bergen.no

Katarina Lundervold, MD

CONTACT

55975045; katarina.lundervold@helse-bergen.no

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Participants and all care providers and investigators are blinded during the trial and during data analysis.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized double-blinded placebo-controlled study with a duration of 1 year. 100 participants randomized to either Placebo (n=50) or NR 2000 mg (n=50).

Study Record Dates

• First Submitted: November 14, 2023
• First Posted: January 17, 2024
• Study Start: January 1, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2030
• Last Updated: January 20, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

NO (2)