FrailtyPhase 2NADageNCT06208527
The NADage Study: Nicotinamide Riboside Replenishment Therapy Against Functional Decline in Aging
A Phase 2 study testing Nicotinamide Riboside (NR) in people with Frailty and Frail Elderly Syndrome, run by Haukeland University Hospital at 2 sites in Norway.
Trial 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. Read more about this study
- Who is it for?
- Ages 75 years and older
- Conditions the study is for
- Frailty, Frail Elderly Syndrome, Frailty Syndrome
- What is being tested?
- Nicotinamide Riboside (NR)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 2 sitesNorway
- Study dates
- Jan 2025to Dec 2030
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 75 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- 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).
Who cannot join
- 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.
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- 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.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Norway2 sites, 2 recruiting
- Not yet recruiting
Haukeland University Hospital
Bergen, Vestland, 5021
Charalampos Tzoulis, PhD, 55975061 ext. +47, charalampos.tzoulis@helse-bergen.no
Katarina Lundervold, MD, 55975045 ext. +47, katarina.lundervold@gmail.com
- Recruiting
Haukeland University Hospital
Bergen, 5021
Charalampos Tzoulis, 55975061 ext. +47, charalampos.tzoulis@helse-bergen.no
Katarina Lundervold, neurosysmedstudier@helse-bergen.no
About this study
Official title: The NADage Study: a Randomized Double-blind Trial of NAD Replenishment Therapy on Aging
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:
Read more
- 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.
Read the detailed description
This study aims to administer 2000 mg of nicotinamide riboside (NR) daily to explore its effects on brain and body metabolism in an elderly, frail population. The research design is a single-center, double-blind, randomized, placebo-controlled approach. Participants will be evenly randomized into two groups in a 1:1 ratio: one to receive a placebo and the other to receive 2000 mg of NR daily. The intervention will last for 52 weeks, during which primary and secondary outcomes will be assessed across and within both groups.
The primary objective is to evaluate the impact of NR on gait speed by comparing the treatment group with the placebo group. Secondary objectives include assessing the safety and tolerability of NR, as well as its clinical effects on physical and cognitive functions, using standardized tests. Furthermore, exploratory objectives will be pursued using various methods such as questionnaires, biosampling, actigraphy, and brain scans. These scans will include 31P-MR-spectrometry to analyze NAD levels in the brain and FDG-PET to assess metabolic network activity. The study will include 100 frail individuals who have provided informed consent. Biological samples to be collected include blood/serum, blood cells, urine, and fecal samples.
Given the previously demonstrated potential of NR in reducing symptoms of Parkinson's disease, this study seeks to expand knowledge of its effects on an elderly, frail population without neurodegenerative disorders. If NR is found to be effective in improving measures of frailty, it could significantly impact societal health and economy, especially considering the extensive socio-economic challenges associated with frailty.
- Conditions
- Frailty, Frail Elderly Syndrome, Frailty Syndrome, Aging
- Being tested
- Nicotinamide Riboside (NR), Placebo
- Keywords
- Frailty, Nicotinamide Riboside, NR, Nicotinamide adenine dinucleotide, NAD, Frail, Aging, Functional decline
- Medical subject headings
- Frailty
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nicotinamide Riboside (NR)Dietary supplement
A total of 2000 mg NR is administered daily for 1 year.
PlaceboOther
Placebo tablet identical in taste, shape and appearance to NR tablets.
| Study group | Role | What they receive |
|---|---|---|
| Placebo group | Placebo comparator | Placebo, no active ingredients. Administered in tablet form twice daily for the duration of the trial (1 year). Receives: Other: Placebo |
| NR group | Experimental | Nicotinamide Riboside (NR) administered in doses of 1000 mg twice daily for the duration of the trial (1 year). Receives: Dietary Supplement: Nicotinamide Riboside (NR) |
What is being measured
The primary outcome is the main question the study is designed to answer.
The between-group (NR vs. Placebo) difference in the change in gait speed.
Gait speed is assessed by the 6-minute walk test (6MWT).
Measured: 52 weeks
Secondary outcomes (4)
Incidence of treatment-emergent adverse events (safety and tolerability).
Monitor the frequency and severity of adverse events (AE).
Measured: 52 weeks
Change in physical performance assessed by the Short Physical Performance Battery (SPPB).
SPPB is performed as an objective measurements on balance, lower extremity strength, and functional capacity through walking and sit to stand test.
Measured: 52 weeks
Change in physical performance assessed by hand grip strength.
Grip strength is measured on the dominant hand with a hydraulic hand-held dynamometer.
Measured: 52 weeks
Change in cognitive function assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) test battery.
The RBANS test battery is composed of tests on immediate memory, visuospatial/constructional abilities, language, attention, and delayed memory. Score range: 40-160. A higher score indicates a better performance.
Measured: 52 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jan 2024
- Study startJan 2025 (estimated)
- Primary completionDec 2027 (estimated)
- Study completionDec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for FrailtyStudies of the same condition, open and under way.
- More trials run by Haukeland University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 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).
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Haukeland University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Charalampos Tzoulis, PhD, Study director, Haukeland University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06208527
- Sponsor's protocol ID
- 2023/680827
- Other IDs
- 2023
- Acronym
- NADage
- Status last verified
- Dec 2024
- First submitted
- 14 Nov 2023
- Last updated
- 20 Jan 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The NADage Study: a Randomized Double-blind Trial of NAD Replenishment Therapy on Aging
- ClinicalTrials.gov ID
- NCT06208527
- Acronym / sponsor ID
- NADage / 2023/680827
- Conditions
- Frailty, Frail Elderly Syndrome, Frailty Syndrome, Aging
- Keywords
- Frailty, Nicotinamide Riboside, NR, Nicotinamide adenine dinucleotide, NAD, Frail, Aging, Functional decline
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Haukeland University HospitalUniversity, hospital or other
- Study start
- Jan 2025 (estimated)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- Dec 2030 (estimated)
- First posted
- 17 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This study aims to administer 2000 mg of nicotinamide riboside (NR) daily to explore its effects on brain and body metabolism in an elderly, frail population. The research design is a single-center, double-blind, randomized, placebo-controlled approach. Participants will be evenly randomized into two groups in a 1:1 ratio: one to receive a placebo and the other to receive 2000 mg of NR daily. The intervention will last for 52 weeks, during which primary and secondary outcomes will be assessed across and within both groups.
The primary objective is to evaluate the impact of NR on gait speed by comparing the treatment group with the placebo group. Secondary objectives include assessing the safety and tolerability of NR, as well as its clinical effects on physical and cognitive functions, using standardized tests. Furthermore, exploratory objectives will be pursued using various methods such as questionnaires, biosampling, actigraphy, and brain scans. These scans will include 31P-MR-spectrometry to analyze NAD levels in the brain and FDG-PET to assess metabolic network activity. The study will include 100 frail individuals who have provided informed consent. Biological samples to be collected include blood/serum, blood cells, urine, and fecal samples.
Given the previously demonstrated potential of NR in reducing symptoms of Parkinson's disease, this study seeks to expand knowledge of its effects on an elderly, frail population without neurodegenerative disorders. If NR is found to be effective in improving measures of frailty, it could significantly impact societal health and economy, especially considering the extensive socio-economic challenges associated with frailty.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- 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).
| Arm | Type | Receives |
|---|---|---|
| Placebo group | Placebo comparator | Other: PlaceboPlacebo, no active ingredients. Administered in tablet form twice daily for the duration of the trial (1 year). |
| NR group | Experimental | Dietary Supplement: Nicotinamide Riboside (NR)Nicotinamide Riboside (NR) administered in doses of 1000 mg twice daily for the duration of the trial (1 year). |
Who may qualify
- Ages
- 75 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (4 listed)
- 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).
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nicotinamide Riboside (NR)A total of 2000 mg NR is administered daily for 1 year. | Dietary supplement | NR group |
| PlaceboPlacebo tablet identical in taste, shape and appearance to NR tablets. | Other | Placebo group |
Primary outcome
The between-group (NR vs. Placebo) difference in the change in gait speed.
Time frame: 52 weeks
Gait speed is assessed by the 6-minute walk test (6MWT).
4 secondary outcomes
Incidence of treatment-emergent adverse events (safety and tolerability).
Time frame: 52 weeks
Change in physical performance assessed by the Short Physical Performance Battery (SPPB).
Time frame: 52 weeks
Change in physical performance assessed by hand grip strength.
Time frame: 52 weeks
Change in cognitive function assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) test battery.
Time frame: 52 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jan 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Charalampos Tzoulis, PhD study director
Haukeland University Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nicotinamide Riboside (NR) in people with Frailty and Frail Elderly Syndrome, run by Haukeland University Hospital at 2 sites in Norway.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 20 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Norway. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Charalampos Tzoulis, PhD (55975061 ext. +47, charalampos.tzoulis@helse-bergen.no), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The between-group (NR vs. Placebo) difference in the change in gait speed. (time frame: 52 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jan 2025.