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

Launched by HAUKELAND UNIVERSITY HOSPITAL · Nov 29, 2023

Keywords

ClinConnect Summary

The NADAPT Study is a clinical trial designed to explore a potential treatment for patients with severe neurological conditions called Progressive Supranuclear Palsy (PSP), Multiple System Atrophy (MSA), and Corticobasal Syndrome (CBS). These diseases can cause serious issues with movement and other body functions, and currently, there are no effective treatments available. The study is testing whether a supplement called Nicotinamide Riboside (NR), taken daily, can improve the health of nerve cells and slow down the progression of these diseases.

To participate in the trial, individuals must be between 30 and 85 years old, have a confirmed diagnosis of one of the three conditions, and be able to walk at least a little on their own or with assistance. About 455 patients from across Norway will be involved, and they will be divided into groups to receive either the NR supplement or a placebo (a sugar pill that looks like the actual treatment but has no active ingredients). The study will last 78 weeks, during which participants will have regular check-ups and will be monitored for any changes in their condition. After the study, participants may also have the option to continue receiving NR in a follow-up study.

Gender

ALL

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.