Recruiting: YES
ClinicalTrials.gov ID: NCT06162013
Ethics approval body/ID: 634814
Type of study: phase II, randomized, double-blind clinical trial
Single/multi-center: multi-center
Participating countries: Norway

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Progressive supranuclear palsy (PSP), Multiple system atrophy (MSA) and corticobasal syndrome (CBS) are severe neurodegenerative diseases with rapid progression and no effective treatment. These diseases have apparent similarities with Parkinson’s disease (PD), but differ inn key symptoms and prevalence. Patients quickly succumb to increasing motor and non-motor symptoms and survival ranges from ~3 years to ~10 years. However, patients are often quickly rendered care-dependent due to their symptoms. Although PSP, MSA and CBD are rare diseases they constitute a major and mostly unadressed challenge to health-care providers due to the severity of disease and lack of treatment. Mitochondrial dysfunction has been suggested as a possible cause of these diseases, as well as in PD. Preclinical and clinical evidence from PD nominates nicotineamide riboside (NR) as a way to boost nicotineamide adenine dinucleotide (NAD) levels in the brain and target multiple disease pathways in neurodegenerative diseases. 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.


Participant must understand the nature of the study and be able to provide written, informed consent.

Male or female aged between 30-85 years at baseline.

123I-Ioflupane dopamine transporter imaging (DAT-scan) or F-DOPA-PET confirming nigrostriatal degeneration (in PSP and MSA, but not necessarily in CBS).

Meet the MDS criteria for possible or probable PSP or MSA, or the consensus criteria for probable or possible CBS.

A time since diagnosis for PSP, MSA, or CBS of ≤ 3 years at baseline.

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.


Any malignancy (other than non-metastatic dermatological conditions) within 5 years of the screening visit (Visit 1) or current clinically significant hematological, endocrine, cardiovascular, renal, hepatic, gastrointestinal, or neurological disease. For the non-cancer conditions, if the condition has been stable for at least the one year before the screening visit (Visit 1) and is judged by the site investigator not to interfere with the subject’s participation in the study, the subject may be included.

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.

Insufficient fluency in local language to complete neuropsychological and functional assessments.

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 any putative disease-modifying agent within 90 days of baseline.

Participated in NAD-replenishment therapy trial during the last 2 years before enrolment.

Alcohol or substance abuse within 1 year prior to visit 1 and deemed to be clinically significant by investigator.

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 results.


To test whether NR is a neuroprotective therapy for atypical parkinsonism, we will perform the NADAPT clinical trial. We 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 3000 mg NR daily or placebo. We will include patients from all Norway. Patients will be followed for 78 weeks with both in-clinic visits and decentralized safety measurements and reporting of patient reported outcomes (PROMs). This allows for regular follow-up, without substantially increasing participation burden for patients and care-persons. 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.


PRIMARY OBJECTIVE: The NADAPT trial has three independent primary objectives, one per cohort/diagnosis. These are to determine whether treatment with NR can delay disease progression in PSP, MSA, or CBS.

SECONDARY OBJECTIVES: To determine whether treatment with NR:


Is safe for PSP, MSA and CBS


Influences the progression of specific motor and non-motor symptoms, and/or the decline in patient quality of life


Delays nigrostriatal degeneration, measured by Ioflupane (123I) (i.e., DAT-scan) 

EXPLORATORY OBJECTIVES: To determine whether treatment with NR:


Delays brain atrophy, measured by volumetric MRI, in representative brain regions (frontal lobe, third ventricle, superior cerebellar peduncle, midbrain, brainstem, and whole brain)


Augments NAD metabolism in the brain and blood of individuals with PSP, MSA or CBS.


Affects brain metabolic patterns as measured by FDG-PET (Only in 30 patients per cohort).


Ameliorates neuroinflammation.


Decreases markers of neuronal injury and PSP-, MSA- or CBS-related pathology.


Impacts gene and protein expression.


Estimated to start on the 1st quarter of 2024

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