N-AD: A Randomized, Double Blind, Parallel Group, Placebo Controlled, Phase 2 Trial of Orally Administered Nicotinamide Riboside Over Two Years as a Potential Disease Modifying Treatment for Alzheimer's Disease

Обзор

The goal of this clinical trial is to learn if orally administered nicotinamide riboside works to slow the progression of early Alzheimer disease in adults. It will also learn about the safety of drug nicotinamide riboside. The main questions it aims to answer are: * Does drug nicotinamide riboside slow the progression of Alzheimer disease as measured by the Clinical Dementia Rating scale. * What medical problems do participants have when taking drug nicotinamide riboside? Researchers will compare drug nicotinamide riboside to a placebo (a look-alike substance that contains no drug) to see if nicotinamide riboside works to treat early Alzheimer disease. Participants will: * Take drug nicotinamide ribosie or a placebo every day for 24 months * Visit the clinic once every 26 weeks for checkups and tests

Вмешательства

• Пищевая добавка Nicotinamide Riboside (NR)
  Nicotinamide Riboside 1000mg administered two times a day. Given as capsules. Duration of the trial; 104 weeks.
• Другое Palacebo
  Placebo drug, administered two times a day. Given as capsules. Duration of the trial; 104 weeks.

Первичные конечные точки

• Disease severity assessed by the Clinical Dementia Rating scale (CDR) sum of boxes. [Срок оценки: From baseline to the end of treatment at 104 weeks.]

Вторичные конечные точки (6)

• Change from baseline in the MoCA score at Week 104. [Срок оценки: From baseline to the end of treatment at 104 weeks.]
• Change from baseline in Amsterdam ADL scale short version (A-IADL-Q-SV) at Week 104. [Срок оценки: From baseline to the end of treatment at 104 weeks]
• Change from baseline in delayed recall performance on the CERAD 10-Word List at Week 104 [Срок оценки: From baseline to the end of treatment at 104 weeks.]
• Change from baseline in executive functioning as measured by Trail-Making Test Part B completion time at Week 104 [Срок оценки: From baseline to the end of treatment at 104 weeks.]
• Change from baseline in verbal fluency as measured by the COWAT (total correct words for F, A, S) at Week 104. [Срок оценки: From baseline to the end of treatment at 104 weeks.]
• Change from baseline in Neuropsychiatric Inventory-Questionnaire (NPI-Q) at Week 104. [Срок оценки: From baseline to the end of treatment at 104 weeks.]

Критерии участия

Критерии включения

• Diagnosis Early clinical AD, e.g. Stage 3 MCI or Stage 4 (mild AD dementia), as defined by the FDA, 2024.
• Biomarker evidence consistent with AD neuropathologic change, defined by CSF markers, i.e. Aβ42 < 1030 ng/L and P-tau181/Aβ42 > 0,023 ng/L and/or T-tau/Aβ42 > 0,28 ng/L\* or AD amyloid biomarker (as determined either by visual reading of amyloid PET scans using an approved ligand
• Diagnosed with AD within 2 years from baseline.
• Capacity to provide written informed consent for study participation defined as Montreal Cognitive Assessment (MoCA) score ≥ 16 or Mini Mental State Evaluation (MMSE) score ≥ 20. MMSE or MoCA must have been performed within 6 months prior to baseline. If there is any doubt regarding the participants capacity to give informed consent, this will be determined by an evaluation by a consultant clinician who is not associated with the N-AD study.
• Global CDR(33) 0.5-1 (inclusive) at enrollment.
• Age 50 to 85 years (inclusive) at the time of enrollment.
• A study partner with sufficient contact to be able to provide data on ADLs and assist the participant in study drug administration. -
• Cholinesterase inhibitors and memantine can be used if stable for 8 weeks prior to baseline visit.

Критерии исключения

• Diagnosis of dementia other than probable AD.
• Abundant vascular pathology, i.e. Fazekas >2. or >3 lacunar infarcts, stroke involving a major vascular territory, severe small vessel, or white matter disease
• More than 1 core feature of dementia with Lewy bodies, i.e; recurrent visual hallucination, cognitive fluctuations, REM sleep behaviour disorder, one or more spontaneous cardinal features of parkinsonism (tremor, rigidity and bradykinesia).
• Comorbidity that precludes study participation or data interpretation.
• Any psychiatric disorder that would interfere with compliance in the study.
• Use of high dose vitamin B3 supplementation within 30 days of baseline.
• Any active neoplastic malignancy (other than non-metastatic dermatological conditions) within two years of the screening visit or current clinically significant haematological, 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 and/or is judged by the site investigator not to interfere with the subject's participation in the study, the subject may be included.
• Inability to undergo MRI or to comply with study procedures.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

Норвегия · 2 центра

• Haraldsplass Deaconess Hospital — Bergen
• Haukeland University Hospital — Bergen

Идентификаторы

NCT: NCT07741071 · 481035

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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