NAD-supplementation in Drug naïve Parkinson's Disease (NAD-PARK)

NAD-PARK: A Double-blinded Randomized Pilot Trial of NAD-supplementation in Drug naïve Parkinson's Disease

1. Primary objective: Determine if NR has an impact on the neurometabolic profile of patients with PD as measured by [18F]Fluorodeoxyglucose (FDG)-positron emission tomography (FDG-PET).
2. Secondary objective: Determine whether high dose oral NR improves motor symptoms associated with PD.
3. Tertiary objectives: determine whether high dose oral NR rectifies NAD metabolism and increases NAD levels in body fluids and muscle tissue.

Study Overview

• Status: Completed
• Conditions: Parkinson Disease; Neurodegenerative Diseases
• Intervention / Treatment: Dietary supplement: Nicotinamide Riboside; Other: Placebo

Detailed Description

Individuals with PD (n=30) will be recruited starting 14/02/2019 from the department of Neurology, Haukeland University Hospital. Only newly diagnosed and drug naïve PD patients are eligible for inclusion. After initial assessment at baseline, the participants will be randomly assigned (1:1) to one of two study groups (n = 15 per group): Nicotamide Riboside (NR) 500 mg x 2/day, or placebo. Participants and investigators will be masked to treatment group. Participants and investigators will be blinded (double blinded). The study will have a 4 week exposure period, during which patients will self-administer NR 500 mg x 2/day, or placebo per os. Patients will not be using any dopaminergic treatment during the study period. During baseline and 4 week follow-up, MDS-UPDRS will be performed as clinical measure. We will also collect blood, cerebral spinal fluid and muscle biopsy from all subjects at baseline and 4 week follow-up. Imaging will be performed using MRI, DAT Scan and FDG-PET at baseline and 4 week follow-up.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Norway
  • Hordaland
    • Bergen, Hordaland, Norway, 5021
      • Haukeland University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Newly diagnosed with PD
2. Drug naïve with respect to dopaminergic treatment
3. Have a clinical diagnosis of idiopathic PD according to the MDS clinical diagnostic criteria for PD

Exclusion Criteria:

1. [¹²³I]FP-CIT single photon emission CT (DaTscan) does not show nigrostriatal degeneration.
2. Magnetic resonance imaging (MRI) suggestive of atypical parkinsonsism.
3. Dementia or other neurological disorder at baseline visit
4. Metabolic, neoplastic, or other physically or mentally debilitating disorder at baseline visit

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: NR Group; Participants receiving Nicotinamide Riboside capsules, 500mg BI'D for 30 days	Dietary supplement: Nicotinamide Riboside; Nicotinamide Riboside capsules 250mg x 2 BID
Placebo Comparator: Placebo Group; Participant receiving Placebo BIDfor 30 days	Other: Placebo; Placebo capsules BID

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PDRP changes from NR use	The primary outcome will be the between-group difference in Parkinson's disease related pattern (PDRP) measured by FDG-PET comparing baseline and 3-4 week follow-up measurement.	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Motoric change of symptoms from NR use	Clinical changes measured by MDS-UPDRS from using NR	4 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine whether high dose oral NR rectifies NAD metabolism in body fluids and muscle tissue.	To measure NAD a liquid chromatography/tandem mass spectrometry will be use (abrv platform for method is LC-MS/MS.) We are interested in change of value of NAD. There is to our knowledge no measured NAD levels of PD patients. See PMID: 29184669 for the same method that we will use.	4 weeks

Collaborators and Investigators

• Sponsor: Haukeland University Hospital
• Investigators: Principal Investigator: Charalampos Tzoulis, PhD, Nevro-Sysmed

Publications and helpful links

General Publications

• Brakedal B, Dölle C, Riemer F, Ma Y, Nido GS, Skeie GO, Craven AR, Schwarzlmüller T, Brekke N, Diab J, Sverkeli L, Skjeie V, Varhaug K, Tysnes OB, Peng S, Haugarvoll K, Ziegler M, Grüner R, Eidelberg D, Tzoulis C. The NADPARK study: A randomized phase I trial of nicotinamide riboside supplementation in Parkinson's disease. Cell Metab. 2022 Mar 1;34(3):396-407.e6. doi: 10.1016/j.cmet.2022.02.001.

Study record dates

Study Major Dates

• Study Start (Actual): March 9, 2019
• Primary Completion (Actual): February 10, 2020
• Study Completion (Actual): February 10, 2020

Study Registration Dates

• First Submitted: December 7, 2018
• First Submitted That Met QC Criteria: January 21, 2019
• First Posted (Actual): January 25, 2019

Study Record Updates

• Last Update Posted (Actual): February 12, 2020
• Last Update Submitted That Met QC Criteria: February 10, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: clinical pilot, Nicotamide Riboside, Parkinson's Disease
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Parkinson Disease; Neurodegenerative Diseases; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Antimetabolites; Micronutrients; Hypolipidemic Agents; Lipid Regulating Agents; Vitamins; Vitamin B Complex; Nicotinic Acids; Niacinamide; Niacin
• Other Study ID Numbers: 2018/597

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Data will only be shared if there is scientific collaboration. Will not be publicaly shared.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No