The NADAPT Study: a Randomized Double-blind Trial of NAD Replenishment Therapy for Atypical Parkinsonism

NCT06162013 | Recruiting Phase 2 DMC

• 1 other identifier: 2023/634814
• Study Type: interventional
• Target: 330
• Locations: 1 country
• Sites: 3

Brief Summary

Progressive supranuclear palsy (PSP), Multiple system atrophy (MSA) and corticobasal syndrome (CBS) are severe neurodegenerative diseases with rapid progression and no effective treatment. Patients quickly succumb to increasing motor and non-motor symptoms and survival ranges from \~3 years to \~10 years. Although PSP, MSA and CBS are rare diseases they constitute a major and mostly unaddressed challenge to health-care providers due to the severity of disease and lack of treatment. The main hypothesis for the NADAPT trial is that oral administration of NR can boost cellular NAD levels in the central nervous system of patients with PSP, MSA and CBS, and rectify metabolism and inhibit neurodegeneration, resulting in delayed disease progression and amelioration of symptoms for these patients. To test whether NR is a neuroprotective therapy for atypical parkinsonism, the investigators will perform the NADAPT clinical trial. The investigators will include 130 patients with Progressive supranuclear palsy (PSP), 165 patients with Multiple system atrophy (MSA) and an indeterminate number of patients with corticobasal syndrome (CBS). The participants will be stratified by disease into three cohorts and randomized to either 3000mg NR daily or placebo. The trial will include patients from all of Norway. Patients will be followed for 78 weeks with both in-clinic visits and decentralized safety measurements and reporting of patient reported outcomes (PROMs). After completion of the 78 weeks follow-up, patients are offered to continue in an open-label NR-only extension study, this extension study will last until follow-up is completed for the last patients in NADAPT.

Conditions

Progressive Supranuclear Palsy; Multiple System Atrophy; Corticobasal Syndrome

Outcome Measures

Primary Outcomes (3)

• PSP Cohort: Between group difference in PSP Rating Scale (PSPRS) total score from baseline to week 78

  Our primary outcome measure for the PSP Cohort is the between group (placebo or NR) difference in Progressive Supranuclear Palsy Rating Scale (PSPRS) total score from baseline to week 78.

  78 weeks

• MSA Cohort: Between group difference in Unified MSA Rating Scale (UMSARS) total score from baseline to week 78

  Our primary outcome measure for the MSA Cohort is the between group (placebo or NR) difference in the Unified Multiple System Atrophy Rating Scale (UMSARS) total score from baseline to week 78.

  78 weeks

• CBS Cohort: Between group difference in PSP Rating Scale (PSPRS) total score from baseline to week 78

  Our primary outcome measure for the CBS Cohort is the between group (placebo or NR) difference in Progressive Supranuclear Palsy Rating Scale (PSPRS) total score from baseline to week 78.

  78 weeks

Secondary Outcomes (9)

• Safety and tolerability

  79 weeks (Trial duration of 78 weeks plus 7 days after last dose of intervention or placebo)

• Specific motor/non-motor symptoms, activities of daily function, and quality of life as measured by the PSPRS

  78 weeks

• Specific motor/non-motor symptoms, activities of daily function, and quality of life as measured by the UMSARS

  78 weeks

• Specific motor/non-motor symptoms, activities of daily function, and quality of life as measured by the UPDRS

  78 weeks

• Specific motor/non-motor symptoms, activities of daily function, and quality of life as measured by the MoCA

  78 weeks

Other Outcomes (13)

• Daily function

  78 weeks

• Brain atrophy

  78 weeks

• Brain NAD metabolism

  78 weeks

Study Arms (2)

Intervention

ACTIVE COMPARATOR

Following our basket trial design, there will be three parallel intervention cohorts (one per disease/cohort)

Dietary Supplement: Nicotinamide Riboside

Placebo

PLACEBO COMPARATOR

Following our basket trial design, there will be three parallel placebo cohorts (one per disease/cohort)

Other: Placebo

Interventions

Nicotinamide Riboside DIETARY_SUPPLEMENT

Nicotinamide Riboside 3000mg/day

Also known as: NR

Intervention

Placebo OTHER

Placebo. Identical in taste and appearance as the intervention.

Placebo

Eligibility Criteria

• Age: 30 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), 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 30-85 years at baseline.
• I-Ioflupane dopamine transporter imaging (DaTSCAN) or FDOPA- PET has been performed. A negative DaTSCAN cannot be more than two years old at baseline.
• Meet the MDS criteria for possible or probable PSP; or
• Meet the MDS criteria for clinically possible or probable MSA; or
• Meet the consensus criteria for probable or possible CBS.
• A baseline PSPRS score of \<40 for PSP, or baseline UMSARS score \< 3 on items: 1, 2, 7-9.
• Score ≥ 20 on the Mini-Mental State Examination (MMSE) at screening.
• Able to ambulate independently or with assistance defined as the ability to take at least 5 steps with a walker (guarding is allowed provided there is no contact) or the ability to take at least 5 steps with the assistance of another person who can only have contact with one upper extremity.

You may not qualify if:

• Insufficient fluency in local language to complete neuropsychological and functional assessments.
• Evidence of differential diagnoses to PSP, MSA or CBS including: PD; dementia with Lewy bodies; Alzheimer's disease; motor neuron disease; history of repeated and/or major stroke; history of repeated and/or severe brain or spinal cord; history of neuroleptic use (except quetiapine) for prolonged period within the last 6 months; history of severe encephalitis; street drug-related parkinsonism; vascular parkinsonism; familial PSP, FTD, or known pathogenic MAPT mutation; prion disease; other neurological disease or MRI findings that could explain the PSP, MSA or CBS symptoms.
• Presence of other significant neurological or psychiatric disorders including (but not limited to) psychotic disorders; severe bipolar or unipolar depression; seizure disorder; tumor or other space-occupying lesion.
• Treatment with/use of NR or any investigational drugs or device, within 90 days of screening.
• A history of alcohol or substance abuse within 1 year prior to baseline (Visit 1) and deemed to be clinically significant by the site investigator
• Any active neoplastic malignancy (other than non-metastatic dermatological conditions) within two years of the screening visit (Visit 0) or current clinically significant hematological, endocrine, cardiovascular, renal, hepatic, gastrointestinal, or neurological disease. Active neoplastic malignancy is defined as having a known malignant focus and/or receiving anti-cancer treatment. For the non-cancer conditions, if the condition has been stable for at least the one year before the screening visit (Visit 0) and/or is judged by the site investigator not to interfere with the subject's participation in the study, the subject may be included.
• Clinically significant laboratory abnormalities at screening that cannot be corrected to baseline and that is deemed incompatible with study participation by investigator.
• History of deep brain stimulator surgery other than sham surgery for deep brain stimulation (DBS) clinical trial.
• History of a clinically significant medical condition that would interfere with the subject's ability to comply with study instructions, would place the subject at increased risk, or might confound the interpretation of the study results.
• Severe dysphagia with inability to swallow study-drug safely at baseline.

Sponsors & Collaborators

• Haukeland University Hospital: lead
• Oslo University Hospital: collaborator
• Akershus Universitetssykehus HF: collaborator
• Vestre Viken Hospital Trust: collaborator
• Sykehuset Ostfold: collaborator
• Nevro Arendal AS: collaborator
• Helse Forde: collaborator
• Helse Fonna: collaborator
• Universitetssykehuset Nord Norge HF: collaborator
• Helse Møre og Romsdal HF: collaborator
• Nordlandssykehuset HF: collaborator
• Elysium Health: collaborator

Study Sites (3)

Oslo University Hospital

Oslo, Oslo County, 0424, Norway

RECRUITING

Haukeland University Hospital

Bergen, Vestland, 5021, Norway

RECRUITING

Vestre Viken HF

Drammen, Norway

RECRUITING

Related Links

• Study website (Norwegian only)

MeSH Terms

Conditions

Supranuclear Palsy, Progressive; Multiple System Atrophy; Corticobasal Degeneration

Interventions

nicotinamide-beta-riboside

Condition Hierarchy (Ancestors)

Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Ophthalmoplegia; Ocular Motility Disorders; Cranial Nerve Diseases; Tauopathies; Neurodegenerative Diseases; Paralysis; Neurologic Manifestations; Eye Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Primary Dysautonomias; Autonomic Nervous System Diseases; Synucleinopathies

Study Officials

• Charalampos Tzoulis, MD, PhD

  Haukeland University Hospital

  STUDY DIRECTOR

Central Study Contacts

Geir Olve Skeie, MD, Dr.med

CONTACT

55975045; geir.olve.skeie@helse-bergen.no

Gard Aasmund Skulstad Johanson, MD

CONTACT

55975106; gard.aasmund.skulstad.johanson@helse-bergen.no

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blinded trial.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 130 patients with PSP, 165 patients with MSA, and an undetermined number of patients with CBS will be stratified into cohorts by disease and randomized 1:1 per disease to receive either 3000mg NR a day or placebo (Fig 1). Follow up will be 18 months and consist of both in-clinic visits and decentralized patient-reported outcomes. NADAPT follows a basket trial design with parallel cohorts, essentially encompassing three trials in one, and drawing added value from the parallel enrolment and follow up.

Study Record Dates

• First Submitted: November 17, 2023
• First Posted: December 8, 2023
• Study Start: March 5, 2024
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: January 10, 2025

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

NO (3)