NAD replenishment therapy for atypical parkinsonism

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

This study is testing if taking a supplement called Nicotinamide Riboside can help people with atypical parkinsonism feel better and slow down their symptoms.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 330 (estimated)
• Ages: 30 Years to 85 Years
• Sex: All
• Sponsor: Haukeland University Hospital (Academic / other)
• Locations: 3 sites (Oslo, Oslo and 2 other locations)
• Trial ID: NCT06162013 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effects of oral Nicotinamide Riboside (NR) on patients with atypical parkinsonism, specifically targeting Progressive Supranuclear Palsy (PSP), Multiple System Atrophy (MSA), and Corticobasal Syndrome (CBS). The study aims to boost cellular NAD levels in the central nervous system, potentially delaying disease progression and alleviating symptoms. A total of 130 patients will be enrolled, and participants will be randomly assigned to receive either NR or a placebo. The trial will assess the neuroprotective effects of NR through various clinical evaluations and imaging techniques.

Who should consider this trial

Good fit: Ideal candidates include adults aged 30-85 diagnosed with PSP, MSA, or CBS who meet specific clinical and imaging criteria.

Not a fit: Patients with a negative DaTSCAN older than two years or those with severe cognitive impairment may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could provide a much-needed treatment option that may slow disease progression and improve quality of life for patients with atypical parkinsonism.

How similar studies have performed: Previous trials investigating NAD replenishment have shown promising results, suggesting potential efficacy in neurodegenerative conditions, although this specific application is novel.

Eligibility criteria

Inclusion Criteria:

1. Participant must understand the nature of the study and be able to provide written, informed consent.
2. Male or female aged 30-85 years at baseline.
3. 123I-Ioflupane dopamine transporter imaging (DaTSCAN) or FDOPA- PET has been performed. A negative DaTSCAN cannot be more than two years old at baseline.
4. Meet the MDS criteria for possible or probable PSP; or
5. Meet the MDS criteria for clinically possible or probable MSA; or
6. Meet the consensus criteria for probable or possible CBS.
7. A baseline PSPRS score of \<40 for PSP, or baseline UMSARS score \< 3 on items: 1, 2, 7-9.
8. Score ≥ 20 on the Mini-Mental State Examination (MMSE) at screening.
9. 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.

Exclusion Criteria:

1. Insufficient fluency in local language to complete neuropsychological and functional assessments.
2. 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.
3. 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.
4. Treatment with/use of NR or any investigational drugs or device, within 90 days of screening.
5. 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
6. 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.
7. Clinically significant laboratory abnormalities at screening that cannot be corrected to baseline and that is deemed incompatible with study participation by investigator.
8. History of deep brain stimulator surgery other than sham surgery for deep brain stimulation (DBS) clinical trial.
9. 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.
10. Severe dysphagia with inability to swallow study-drug safely at baseline.

Where this trial is running

Oslo, Oslo and 2 other locations

• Oslo University Hospital — Oslo, Oslo, Norway (Recruiting)
• Haukeland University Hospital — Bergen, Vestland, Norway (Recruiting)
• Vestre Viken HF — Drammen, Norway (Recruiting)

Study contacts

• Study coordinator: Geir Olve Skeie, MD, Dr.med

Conditions Progressive Supranuclear Palsy; Multiple System Atrophy; Corticobasal Syndrome