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