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| Name | Class |
|---|---|
| Oslo University Hospital | OTHER |
| University Hospital, Akershus | OTHER |
| Ostfold Hospital Trust | OTHER |
| Førde Hospital Trust |
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NOPARK is a double-blinded randomized controlled phase II trial, with the aim to assess the efficacy of nicotinamide adenine dinucleotide (NAD)-replenishment therapy in the form of oral nicotinamide riboside (NR) in delaying the progression of early Parkinson's disease (PD). A total of 400 persons with early stage Parkinson's disease will be enrolled, randomized on nicotinamide riboside (NR) 500mg x 2 per day or placebo, and followed for 52 weeks.
NOPARK is a multi-center, double-blinded randomized controlled trial, with the aim to assess the efficacy of NAD-replenishment therapy in the form of oral nicotinamide riboside (NR) in delaying the progression of early Parkinson's disease (PD). Individuals with PD (n = 400) will be recruited from multiple centers across Norway. Eligible participants must have been diagnosed with PD within 2 years of study enrollment and meet the trial's inclusion criteria. All participants will be given a standard PD-treatment regimen comprising selegiline 10 mg/day and oral levodopa (Sinemet or Madopar) at a dose of 100mg x 3, 150mg x3, or 200mg x 3 per day. The PD-treatment regimen will be frozen at baseline and remain stable throughout the duration of the study. At baseline, participants will be randomized on a 1:1 ratio on either nicotinamide riboside (NR) 500mg x 2 per day or placebo. Both the participants and the investigators will be blinded. The trial duration will be 52 weeks, during which participants will be assessed at baseline, 13, 26, 39 and 52 weeks. Measures include clinical evaluation using established scales for motor and non-motor dysfunction, as well as quality of life, 123I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) nortropane ([¹²³I]FP-CIT) single photon emission tomography (DaTscan), magnetic resonance imaging (MRI) of the brain, blood safety tests, and blood sampling for metabolomics, transcriptomics, and other exploratory analyses. The primary outcome of the study is the total score of the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Nicotinamide Riboside | Experimental | nicotinamide riboside, 1000mg daily for the duration of the trial (52 weeks). Dosage form is capsules. |
|
| Placebo Comparator | Placebo Comparator | Placebo capsules, no active ingredients. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Nicotinamide Riboside | Dietary Supplement | Nicotinamide Riboside 500mg administered two times a day. Given as capsules. Duration of the trial; 52 weeks. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Disease severity assessed by the total MDS-UPDRS (Movement Disorder Society Unified Parkinson's Disease rating Scale): sum of subsections I, II, and III | The Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) assesses motor and non-motor symptoms of PD through four parts, with individual items rated on a 0-4 scale. Subscores are summed to provide a total score ranging from 0 to 260, with higher scores indicating greater disability. The primary outcome will be the MDS-UPDRS Total Score (sum of parts I, II, and III). | From baseline to the end of treatment at 52 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Severity of motor symptoms in PD. | Change from baseline in the MDS-UPDRS Part III in the ON-medication state. | From baseline to the end of treatment at 52 weeks |
| Severity of dopaminergic nigrostriatal denervation, assessed by [¹²³I]FP-CIT single photon emission CT (DaTscan) |
| Measure | Description | Time Frame |
|---|---|---|
| brain nicotinamide adenine dinucleotide (NAD) levels | Change from baseline in brain NAD/ATP-α ratio measured by 31 Phosphorus magnetic resonance spectroscopy (31P-MRS) in the posterior brain (encompassing the occipital, parietooccipital and posterior parts of the temporal cortex). | From baseline to the end of treatment at 52 weeks |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Charalampos Tzoulis, MD, PhD | Haukeland University Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Bodø Hospital | Bodø | Nordland | Norway | |||
| Arendal Hospital |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| SAP | No | Yes | No | Statistical Analysis Plan | Sep 18, 2025 | Sep 22, 2025 | SAP_000.pdf |
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| ID | Term |
|---|---|
| D010300 | Parkinson Disease |
| ID | Term |
|---|---|
| D020734 | Parkinsonian Disorders |
| D001480 | Basal Ganglia Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| ID | Term |
|---|---|
| C018613 | nicotinamide-beta-riboside |
| D009243 | NAD |
| ID | Term |
|---|---|
| D000227 | Adenine Nucleotides |
| D011685 | Purine Nucleotides |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
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| OTHER |
| Helse Fonna | OTHER |
| Molde Hospital | OTHER |
| Bodø sykehus | UNKNOWN |
| Sorlandet Hospital HF | OTHER_GOV |
| Drammen sykehus | OTHER |
| University Hospital of North Norway | OTHER |
Randomized double-blinded study. N = 400 participants are randomized in a 1:1 ratio to either nicotinamide riboside (500 mg x 2 per day) or placebo.
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Study participants and investigators are blinded.
|
| Placebo | Other | Placebo drug, administered two times a day. Given as capsules. Duration of the trial; 52 weeks. |
|
Change from baseline in the mean striatal binding ratio (SBR) of the putamen, bilaterally, as measured [¹²³I]FP-CIT Single-Photon Emission Computed Tomography (SPECT) Imaging of the Dopamine Transporter (DaT, DaTscan). |
| From baseline to the end of treatment at 52 weeks |
| Severiy of non-motor symptoms in daily living in PD | Change from baseline in the MDS-UPDRS Part I in the ON-medication state | From baseline to the end of treatment at 52 weeks |
| Severity of motor aspects of experiences of daily living in PD. | Change from baseline in the MDS-UPDRS Part II | From baseline to the end of treatment at 52 weeks |
| Severity of non-motor symptoms of PD assessed by the Non-Motor Symptoms Assessment Scale | Change from baseline in the NMSS Score in the ON-medication state. Non-Motor Symptoms Scale (NMSS) has 30 items, score range is 0-360 with higher scores indicating a worse outcome. | From baseline to the end of treatment at 52 weeks |
| Change in the clinical severity of cognitive decline assessed by the Montreal Cognitive Assessment (MoCA) scale | Montreal Cognitive Assessment (MoCA), score range is 0-30 with lower scores indicating a worse outcome. | From baseline to the end of treatment at 52 weeks |
| Change in quality of life assessed by the EuroQuality of Life Five Dimensions (EQ-5D-5L) questionnaire. | Quality of Life assessment (EuroQuality of Life Five Dimensions - EQ-5D-5L). | From baseline to the end of treatment at 52 weeks |
| Hoehn and Yahr stage of PD | Hoehn and Yahr scale distinguishes between five stages in PD: Stage 1: Unilateral disease; Stage 2: Bilateral disease without impairment of balance; Stage 3: Bilateral disease with postural instability but physically independent; Stage 4: Severe disability; still able to walk or stand unassisted; Stage 5: Confinement to bed or wheelchair unless aided. | From baseline to the end of treatment at 52 weeks |
| systemic nicotinamide adenine dinucleotide (NAD) metabolism |
Change from baseline in the NAD metabolome in whole blood or PBMC, measured by liquid chromatography mass spectrometry (LC-MS): Nicotinamide adenine dinucleotide oxidized (NAD+), Nicotinamide adenine dinucleotide reduced (NADH), NAD+/NADH ratio, total NAD (sum of NAD+ and NADH), Nicotinamide adenine dinucleotide phosphate oxidized (NADP+), Nicotinamide adenine dinucleotide phosphate reduced (NADPH), NADP+/NADPH ratio, total NADP (sum of NADP+ and NADPH, 1-methyl nicotinamide (Me-Nam), nicotinic acid-adenine dinucleotide (NAAD), N1-methyl-2-pyridone-5-carboxamide (Me-2-PY), Nicotinamide (Nam), Nicotinamide N-oxide (Nam N-oxide), ADP-ribose (ADPR), Nicotinic acid riboside (NAR), Nicotinamide riboside (NR), Nicotinamide mononucleotide (NMN), Nicotinic acid (NA). |
| From baseline to the end of treatment at 52 weeks |
| neurofilament light-chain (NfL) levels | Change from baseline in serum neurofilament light-chain (NfL) levels, measured by Simoa analysis. | From baseline to the end of treatment at 52 weeks |
| Safety and tolerablity | Report of all Adverse Events (AE) of moderate or severe intensity and Serious Adverse Events (SAE). | From baseline to the end of treatment at 52 weeks |
| Arendal |
| Norway |
| Haukeland University Hospital | Bergen | Norway |
| Vestre Viken Hospital | Drammen | Norway |
| Førde sykehus | Førde | Norway |
| Haugesund Hospital | Haugesund | Norway |
| Molde sjukehus | Molde | Norway |
| Akershus university hospital | Oslo | Norway |
| Oslo University Hospital | Oslo | Norway |
| University Hospital of North Norway | Tromsø | Norway |
| Østfold Hospital | Fredrikstad | Østland | Norway |
| D009422 | Nervous System Diseases |
| D009069 | Movement Disorders |
| D000080874 | Synucleinopathies |
| D019636 | Neurodegenerative Diseases |
| D000072471 |
| Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D003067 | Coenzymes |
| D045762 | Enzymes and Coenzymes |
| D009711 | Nucleotides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D012265 | Ribonucleotides |