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

What Was Tested

This registered phase 2 trial tested NAD+.

It had two arms (groups): Intervention (active comparator) and Placebo (placebo comparator).

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

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

The registry classes the interventions as dietary supplement and other.

More on the Plan

Background/Rationale: Atypical parkinsonian syndromes (APS) are rapidly progressive, debilitating, and incurable neurodegenerative diseases, including progressive supranuclear palsy (PSP), multiple system atrophy (MSA) and corticobasal syndrome (CBS).

These are classified as rare and orphan disorders according to EU regulation, with a reported prevalence of 7/100,000 for PSP, 4.4/100,000 for MSA, and 0.6-1/100,000 for CBS, although accurate numbers for CBS are lacking.

Currently, there are no neuroprotective therapies able to delay the progression of APS.

Despite being a source of morbidity and mortality comparable to amyotrophic lateral sclerosis (ALS), there are currently no clinical treatment studies on PSP, MSA, or CBS in Norway, and very few initiatives globally.

Who Took Part

The registry lists 330 planned participants were the target.

It was open to people of any sex aged from 30 years up to 85 years.

Healthy volunteers were not accepted; participants needed the condition being studied.

Examples of who could join: 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.

The full record lists 9 inclusion and 10 exclusion criteria; among the exclusions: insufficient fluency in local language to complete neuropsychological and functional assessments; treatment with/use of nr or any investigational drugs or device, within 90 days of screening; history of deep brain stimulator surgery other than sham surgery for deep brain stimulation (dbs) clinical trial.

How the Study Was Run

The set-up was randomized, parallel-group and quadruple-blind.

Random assignment meant chance, not the researchers, decided who got NAD+ and who got the comparison, which limits bias.

The NAD+ group and the comparison group ran side by side rather than switching.

Neither the participants nor the staff measuring them knew who was on NAD+, so expectations could not easily colour the readings.

Those kept unaware of assignments: participant, care provider, investigator and outcomes assessor.

It started in 2024-03-05 with completion listed for 2028-12.

It ran at 3 sites in Norway (3).

Its stated primary purpose is treatment.

What Was Measured

The main thing measured (primary outcome): PSP Cohort: Between group difference in PSP 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 (time frame: 78 weeks). CBS Cohort: Between group difference in PSP Rating Scale (PSPRS) total score from baseline to week 78 (time frame: 78 weeks).

It also tracked 9 secondary outcomes, for example Safety and tolerability, Specific motor/non-motor symptoms, activities of daily function, and quality of life as measured by the PSPRS, Specific motor/non-motor symptoms, activities of daily function, and quality of life as measured by the UMSARS, Specific motor/non-motor symptoms, activities of daily function, and quality of life as measured by the UPDRS, Specific motor/non-motor symptoms, activities of daily function, and quality of life as measured by the MoCA and Specific motor/non-motor symptoms, activities of daily function, and quality of life as measured by the SEADL.

What This Means in Plain Language

Put simply, this is a phase 2, randomized trial of NAD+ in 330 people.

It is still recruiting; no results are posted to the registry yet, so nothing here describes outcomes.

More context: the NAD+ compound page, all human trials.