Parkinson DiseaseNR-SAFENCT05344404
NR-SAFE: Safety of High-dose Nicotinamide Riboside (NR) in Parkinson's Disease
A study testing Nicotinamide Riboside in people with Parkinson Disease, run by Haukeland University Hospital at 1 site in Norway.
Trial summary
NR-SAFE is a double-blinded randomized safety study aiming to determine the safety and tolerability of nicotinamide riboside (NR) at a daily dose of 3000mg, in individuals with Parkinson's disease (PD). Read more about this study
- Who is it for?
- Ages 35 years and older
- Conditions the study is for
- Parkinson Disease
- What is being tested?
- Nicotinamide Riboside
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteNorway
- Study dates
- 29 Apr 2022to 1 Jul 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 35 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age equal to or greater than 35 years and lower than 100 years at time of enrollment.
- Clinical diagnosis of idiopathic PD according to the MDS criteria.
- Hoehn and Yahr score < 4 at enrolment.
Who cannot join
- Dementia or other neurodegenerative disorder at baseline visit.
- Any psychiatric disorder that would interfere with compliance in the study.
- Any severe somatic illness that would make the individual unable to comply and participate in the study.
- Use of high dose vitamin B3 supplementation within 30 days of enrollment.
- Metabolic, neoplastic, or other physically or mentally debilitating disorder at baseline visit.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: NR-SAFE: a Safety Study Investigating Treatment With High-dose Nicotinamide Riboside (NR) in Parkinson's Disease
NR-SAFE is a double-blinded randomized safety study aiming to determine the safety and tolerability of nicotinamide riboside (NR) at a daily dose of 3000mg, in individuals with Parkinson's disease (PD).
The investigators recently reported the results of the NADPARK study (ClinicalTrials.gov: NCT03816020), a phase I randomized, double-blinded trial, assessing the tolerability, cerebral bioavailability and molecular effects of NR therapy, 1000mg daily, in PD. The NADPARK study showed that NR 1000mg daily was well tolerated and led to a significant, but variable, increase in cerebral NAD levels (measured by 31phosphorous magnetic resonance spectroscopy, 31P-MRS) and related metabolites in the cerebrospinal fluid (CSF). NR recipients showing increased brain NAD levels exhibited altered cerebral metabolism, measured by 18fluoro-deoxyglucose positron emission tomography (FDG-PET), and this was associated with mild clinical improvement. The results of the NADPARK trial nominate NR as a potential neuroprotective therapy for PD, warranting further investigation in larger trials.
Read more
It is plausible that any beneficial effects of NR in PD may be dose-dependent and more pronounced at higher doses. NR doses of up to 2000mg daily have been tested in healthy humans with no signs of toxicity. However, the safety and tolerability of even higher doses is untested. To enable clinical studies assessing higher doses, the investigators will assess the safety and tolerability of an oral dose of 3000 mg NR daily.
NR-SAFE will recruit 20 participants with PD and randomize them 1:1 to either NR 3000mg daily or placebo for a total duration of 4 weeks.
Read the detailed description
NR-SAFE is a double-blinded randomized safety study aiming to determine the safety and tolerability of nicotinamide riboside (NR) at a daily dose of 3000mg, in individuals with Parkinson's disease (PD). Individuals with PD (n = 20) will be recruited starting April 2022. Participants will be randomized 1:1 to either NR 3000mg daily (1500mg x 2) or placebo per os for a total duration of 4 week. Both the participants and the investigators will be blinded.
Primary Objective:
To determine the safety of oral NR 3000mg daily for a period of 4 weeks in individuals with Parkinson's disease (PD). Safety is defined as the absence of clinically significant NR-associated moderate or severe adverse events (AE).
Secondary Objectives:
- Determine whether oral NR 3000 mg daily is associated with mild AE.
- Assess the effects of oral NR 3000 mg daily on the NAD metabolome in blood and urine.
- Assess the effects of oral NR 3000 mg daily on clinical severity of PD, measured by UPDRS.
Exploratory Objectives:
- Assess the effects of oral NR 3000 mg daily on serum homocysteine levels.
- Assess the effects of oral NR 3000 mg daily on fasting blood glucose and serum insulin levels.
Procedures:
After the baseline visit, participants will be reassessed in person on day 5, 7, 14, 21 and 28 by one of the neurologists involved in the study and by telephone on day 3 and 35 by the study nurse. Participants will be screened for any adverse effects on each of these consultations. Drawing of blood samples will be performed on baseline and day 3, 5, 7, 14, 21 and 28. Clinical examination and measurement of vital parameters will be performed on baseline and on day 7, 14, 21 and 28.
Primary Outcome:
Incidence of treatment-associated moderate and severe AEs.
Secondary Outcomes:
- Between-group difference in treatment associated mild AEs.
- Between-group difference in changes of the NAD metabolome in blood and urine, measured by mass spectrometry (LC-MS/MS Q-Exactive HF).
- Between-group difference in change of clinical severity of PD, measured by UPDRS.
Exploratory Outcomes:
- Between-group difference in the change of serum homocysteine levels.
- Between-group difference in the change of fasting blood glucose and serum insulin levels.
- Conditions
- Parkinson Disease
- Being tested
- Nicotinamide Riboside, Placebo
- Keywords
- Parkinson's disease, NAD metabolism, Mitochondria, Nicotinamide Riboside
- Medical subject headings
- Parkinson Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nicotinamide RibosideDietary supplement
Also called Niagen, NR
3000mg total daily. Administered in capsule form in doses of 1500mg twice daily for the duration of the trial (4 weeks).
PlaceboDietary supplement
Placebo drug. Administered in tablet form twice daily for the duration of the trial (4 weeks).
| Study group | Role | What they receive |
|---|---|---|
| Nicotinamide Riboside | Experimental | Nicotinamide riboside 3000mg daily for the duration of the trial (4 weeks). Administered in tablet form in doses of 1500mg twice daily. Receives: Dietary Supplement: Nicotinamide Riboside |
| Placebo | Placebo comparator | Placebo, no active ingredients. Administered in tablet form twice daily for the duration of the trial (4 weeks). Receives: Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of treatment-associated moderate and severe adverse events (AEs).
The incidence of treatment-associated moderate and severe adverse events (AEs) will be assessed.
Measured: 4 weeks.
Secondary outcomes (3)
Incidence of treatment-associated mild adverse events (AEs).
The incidence of treatment-associated mild adverse events (AEs) will be assessed.
Measured: 4 weeks.
Between-group (NR vs placebo) difference in changes of the NAD metabolome in blood and urine, measured by mass spectrometry (LC-MS/MS Q-Exactive HF)
The concentration of NAD metabolites, such as NAD, NAAD, NAM, meNAM, etc, will be determined in blood (snap-frozen EDTA) and urin using liquid chromatography mass spectrometry (LC-MS/MS Q-Exactive HF). The change in the concentration of NAD metabolites in the NR and placebo group, as well as the between-group (NR vs placebo) difference in the change of the concentration of NAD metabolites will be assessed.
Measured: 4 weeks.
Between-group (NR vs placebo) difference in change of clinical severity of PD, measured by UPDRS.
The change in total UPDRS in the NR and placebo group, as well as the between-group (NR vs placebo) difference in the change of total UPDRS will be assessed.
Measured: 4 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Apr 2022
- Study start29 Apr 2022
- Primary completion1 Jul 2022
- Study completion1 Jul 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Parkinson DiseaseStudies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized double-blinded study. 20 participants randomized in 1:1 ratio to either vitamin supplementation or placebo.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Haukeland University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Charalampos Tzoulis, MD, PhD, Principal investigator, Haukeland University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05344404
- Sponsor's protocol ID
- 2021/379218
- Acronym
- NR-SAFE
- Status last verified
- Mar 2022
- First submitted
- 19 Apr 2022
- Last updated
- 9 Aug 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Berven H, Kverneng S, Sheard E, Sognen M, Af Geijerstam SA, Haugarvoll K, Skeie GO, Dolle C, Tzoulis C. NR-SAFE: a randomized, double-blind safety trial of high dose nicotinamide riboside in Parkinson's disease. Nat Commun. 2023 Nov 28;14(1):7793. doi: 10.1038/s41467-023-43514-6.
PubMed 38016950
Study at a glance
From the registry record, last updated by the sponsor on 9 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- NR-SAFE: a Safety Study Investigating Treatment With High-dose Nicotinamide Riboside (NR) in Parkinson's Disease
- ClinicalTrials.gov ID
- NCT05344404
- Acronym / sponsor ID
- NR-SAFE / 2021/379218
- Conditions
- Parkinson Disease
- Keywords
- Parkinson's disease, NAD metabolism, Mitochondria, Nicotinamide Riboside
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Haukeland University HospitalUniversity, hospital or other
- Study start
- 29 Apr 2022 (actual)
- Primary completion
- 1 Jul 2022 (actual)
- Study completion
- 1 Jul 2022 (actual)
- First posted
- 25 Apr 2022 (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.
NR-SAFE is a double-blinded randomized safety study aiming to determine the safety and tolerability of nicotinamide riboside (NR) at a daily dose of 3000mg, in individuals with Parkinson's disease (PD).
The investigators recently reported the results of the NADPARK study (ClinicalTrials.gov: NCT03816020), a phase I randomized, double-blinded trial, assessing the tolerability, cerebral bioavailability and molecular effects of NR therapy, 1000mg daily, in PD. The NADPARK study showed that NR 1000mg daily was well tolerated and led to a significant, but variable, increase in cerebral NAD levels (measured by 31phosphorous magnetic resonance spectroscopy, 31P-MRS) and related metabolites in the cerebrospinal fluid (CSF). NR recipients showing increased brain NAD levels exhibited altered cerebral metabolism, measured by 18fluoro-deoxyglucose positron emission tomography (FDG-PET), and this was associated with mild clinical improvement. The results of the NADPARK trial nominate NR as a potential neuroprotective therapy for PD, warranting further investigation in larger trials.
It is plausible that any beneficial effects of NR in PD may be dose-dependent and more pronounced at higher doses. NR doses of up to 2000mg daily have been tested in healthy humans with no signs of toxicity. However, the safety and tolerability of even higher doses is untested. To enable clinical studies assessing higher doses, the investigators will assess the safety and tolerability of an oral dose of 3000 mg NR daily.
NR-SAFE will recruit 20 participants with PD and randomize them 1:1 to either NR 3000mg daily or placebo for a total duration of 4 weeks.
Detailed description
NR-SAFE is a double-blinded randomized safety study aiming to determine the safety and tolerability of nicotinamide riboside (NR) at a daily dose of 3000mg, in individuals with Parkinson's disease (PD). Individuals with PD (n = 20) will be recruited starting April 2022. Participants will be randomized 1:1 to either NR 3000mg daily (1500mg x 2) or placebo per os for a total duration of 4 week. Both the participants and the investigators will be blinded.
Primary Objective:
To determine the safety of oral NR 3000mg daily for a period of 4 weeks in individuals with Parkinson's disease (PD). Safety is defined as the absence of clinically significant NR-associated moderate or severe adverse events (AE).
Secondary Objectives:
- Determine whether oral NR 3000 mg daily is associated with mild AE.
- Assess the effects of oral NR 3000 mg daily on the NAD metabolome in blood and urine.
- Assess the effects of oral NR 3000 mg daily on clinical severity of PD, measured by UPDRS.
Exploratory Objectives:
- Assess the effects of oral NR 3000 mg daily on serum homocysteine levels.
- Assess the effects of oral NR 3000 mg daily on fasting blood glucose and serum insulin levels.
Procedures:
After the baseline visit, participants will be reassessed in person on day 5, 7, 14, 21 and 28 by one of the neurologists involved in the study and by telephone on day 3 and 35 by the study nurse. Participants will be screened for any adverse effects on each of these consultations. Drawing of blood samples will be performed on baseline and day 3, 5, 7, 14, 21 and 28. Clinical examination and measurement of vital parameters will be performed on baseline and on day 7, 14, 21 and 28.
Primary Outcome:
Incidence of treatment-associated moderate and severe AEs.
Secondary Outcomes:
- Between-group difference in treatment associated mild AEs.
- Between-group difference in changes of the NAD metabolome in blood and urine, measured by mass spectrometry (LC-MS/MS Q-Exactive HF).
- Between-group difference in change of clinical severity of PD, measured by UPDRS.
Exploratory Outcomes:
- Between-group difference in the change of serum homocysteine levels.
- Between-group difference in the change of fasting blood glucose and serum insulin levels.
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 study. 20 participants randomized in 1:1 ratio to either vitamin supplementation or placebo.
| Arm | Type | Receives |
|---|---|---|
| Nicotinamide Riboside | Experimental | Dietary Supplement: Nicotinamide RibosideNicotinamide riboside 3000mg daily for the duration of the trial (4 weeks). Administered in tablet form in doses of 1500mg twice daily. |
| Placebo | Placebo comparator | Dietary Supplement: PlaceboPlacebo, no active ingredients. Administered in tablet form twice daily for the duration of the trial (4 weeks). |
Who may qualify
- Ages
- 35 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age equal to or greater than 35 years and lower than 100 years at time of enrollment.
- Clinical diagnosis of idiopathic PD according to the MDS criteria.
- Hoehn and Yahr score < 4 at enrolment.
Key exclusion criteria (5 listed)
- Dementia or other neurodegenerative disorder at baseline visit.
- Any psychiatric disorder that would interfere with compliance in the study.
- Any severe somatic illness that would make the individual unable to comply and participate in the study.
- Use of high dose vitamin B3 supplementation within 30 days of enrollment.
- Metabolic, neoplastic, or other physically or mentally debilitating disorder at baseline visit.
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 RibosideAlso: Niagen, NR3000mg total daily. Administered in capsule form in doses of 1500mg twice daily for the duration of the trial (4 weeks). | Dietary supplement | Nicotinamide Riboside |
| PlaceboPlacebo drug. Administered in tablet form twice daily for the duration of the trial (4 weeks). | Dietary supplement | Placebo |
Primary outcome
Incidence of treatment-associated moderate and severe adverse events (AEs).
Time frame: 4 weeks.
The incidence of treatment-associated moderate and severe adverse events (AEs) will be assessed.
3 secondary outcomes
Incidence of treatment-associated mild adverse events (AEs).
Time frame: 4 weeks.
Between-group (NR vs placebo) difference in changes of the NAD metabolome in blood and urine, measured by mass spectrometry (LC-MS/MS Q-Exactive HF)
Time frame: 4 weeks.
Between-group (NR vs placebo) difference in change of clinical severity of PD, measured by UPDRS.
Time frame: 4 weeks.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Aug 2022.
- Derived from this study: PubMed 38016950Berven H, Kverneng S, Sheard E, Sognen M, Af Geijerstam SA, Haugarvoll K, Skeie GO, Dolle C, Tzoulis C. NR-SAFE: a randomized, double-blind safety trial of high dose nicotinamide riboside in Parkinson's disease. Nat Commun. 2023 Nov 28;14(1):7793. doi: 10.1038/s41467-023-43514-6.
- 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. This study is not recruiting at the moment.
Charalampos Tzoulis, MD, PhD principal investigator
Haukeland University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Nicotinamide Riboside in people with Parkinson Disease, run by Haukeland University Hospital at 1 site 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 3 inclusion and 5 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: finished, as of the sponsor's last update on 9 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of treatment-associated moderate and severe adverse events (AEs). (time frame: 4 weeks.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05344404, which also lists 1 linked publication.
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 9 Aug 2022.