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

ConditionsProgressive Supranuclear Palsy Multiple System Atrophy Corticobasal Syndrome

Trial statusRecruiting

Trial phasePhase 2

Trial typeInterventional

Biological sexAll

Age30-85

SponsorHaukeland University Hospital

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

123I-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

Disqualifiers

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.

Trial design

Design model

Parallel

Treatments tested in this trial

Nicotinamide Riboside
Dietary supplement
Nicotinamide Riboside 3000mg/day
Placebo
Other intervention
Placebo. Identical in taste and appearance as the intervention.

Treatment groups

330 Participants

are divided into 2 treatment groups

Group A: InterventionActive comparator 1 intervention

Group B: PlaceboPlacebo comparator 1 intervention

Trial outcomes

Primary outcomes

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.

Time frame

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.

Time frame

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.

Time frame

78 weeks

Secondary outcomes

Safety and tolerability

Monitor frequency and severity of adverse events (AE)

Time frame

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

Measured by individual items of the PSPRS

Time frame

78 weeks

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

Measured by individual items of the UMSARS

Time frame

78 weeks

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

Measured by individual items of the Movement disorders society unified parkinson's disease rating scale (UPDRS)

Time frame

78 weeks

Other outcomes

Daily function

Real-time wearable sensor-based data to evaluate symptoms of disease/disease burden in the home.

Time frame

78 weeks

Brain atrophy

MRI-volumetric measurements in the frontal lobe, third ventricle, superior cerebellar peduncle, midbrain, brainstem, and whole brain.

Time frame

78 weeks

Brain NAD metabolism

NAD levels in the brain parenchyma measured by 31P-MRS, and NAD metabolome in CSF.

Time frame

78 weeks

Markers of neuroinflammation

Levels of selected inflammatory cytokines in serum and CSF.

Time frame

78 weeks

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Haukeland University Hospital

Lead sponsor

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

Source ClinicalTrials.gov

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