N-DOSE AD: A Dose Optimization Trial of Nicotinamide Riboside in Alzheimer's Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 80
- 试验地点
- 4
- 主要终点
- Cerebral NAD levels measured by 31P-MRS
研究概览
简要总结
The goal of this double-blinded placebo-controlled randomized trial is to determine the optimal dose of nicotinamide riboside (NR), in individuals with Alzheimer's disease (AD).
The main questions the N-DOSE AD trial aims to answer are:
What dose of nicotinamide riboside (NR) is required to achieve maximal cerebral nicotinamide adenine dinucleotide (NAD) increase, measured by 31P-magnetic resonance spectroscopy (MRS) or cerebrospinal fluid (CSF) metabolomics)?
What dose of nicotinamide riboside (NR) is required to achieve maximal alteration in the cerebral metabolism patterns, measured by fluorodeoxyglucose-positron emission tomography (FDG-PET)?
What dose of nicotinamide riboside (NR) will have optimal effect in the absence of unacceptable toxicity?
Participants will be asked to do participate in:
Clinical examinations
Cognitive assessments
Lumbar puncture
Magnetic resonance imaging - positron emission tomography (MRI-PET) scannings
Biosampling
They'll be given placebo, 1000 mg NR or escalating doses of NR (1000 mg - 2000 mg - 3000 mg) over 12 weeks.
详细描述
N-DOSE AD is a double-blinded placebo-controlled randomized trial aiming to determine the optimal biological dose (OBD) of nicotinamide riboside (NR), in individuals with Alzheimer's disease (AD).
Individuals with AD (n = 80) will be recruited starting November 2022. Participants will be randomized 1:1:2 to either placebo group (n = 20) or NR 1000mg daily (n = 20) for 12 weeks or to a dose-escalation group where NR 1000mg daily will be administered week 1-4, NR 2000mg daily week 5-8 and NR 3000mg daily week 9-12 (n =40). Both the participants and the investigators will be blinded.
- Primary Objective:
-- To compare the effect of orally administered nicotinamide riboside (NR), escalated to 1500 mg twice per day (3000 mg/day) in the dose escalation group (DE-group) - versus stable dosing of 500 mg twice per day (1000 mg/day) in the dose-stable group (DS-group) on cerebral NAD levels, at week 12.
-
Secondary Objectives:
-
To assess the dose-response relationship between NR dose (1000 mg, 2000 mg, 3000 mg per day) and changes in cerebral NAD levels from baseline to weeks 4, 8 and 12.
-
To compare the effectiveness of orally administered nicotinamide riboside (NR) 1500 mg twice per day versus 500 mg twice per day in augmenting the NAD-metabolome in the central nervous system (CNS) at week 12.
-
Safety Objectives
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
Both participants and all investigators are blinded during the trial and during data analysis.
入排标准
- 年龄范围
- 50 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The following condition must apply to the prospective patient at screening prior to receiving study agent:
- •Diagnosis of probable Alzheimer Disease (AD) according to the core clinical criteria updated in the National Institute on Aging (NIA) and Alzheimer's Association guidelines.
- •Biomarker evidence consistent with AD neuropathologic change, defined by cerebrospinal fluid (CSF) markers.
- •Diagnosed with AD within two years from enrollment.
- •Clinical Dementia Rating (CDR) 0.5-1 (inclusive) at enrollment.
- •Age 50 to 85 years (inclusive) at the time of enrollment.
- •A study partner (i.e. a family member or a friend) able to provide study data and assist the participant in the study drug administration, i.e. contact ≥ 3 times weekly.
- •Capacity to provide written informed consent for study participation defined as Montreal Cognitive Assessment (MoCA) score ≥ 16 or Mini Mental State Evaluation (MMSE) score ≥
- •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 we will ask for an independent evaluation by a consultant clinician who is not associated with the N-DOSE AD study.
- •Cholinesterase inhibitors and memantine can be used if stable for 8 weeks prior to baseline visit.
- •Able to undergo lumbar puncture.
- •Able to undergo magnetic resonance imaging (MRI)
排除标准
- •Patients will be excluded from the study if they meet any of the following criteria:
- •Diagnosis of dementia other than probable AD.
- •Comorbidity that precludes study participation or data interpretation.
- •Any psychiatric disorder that would interfere with compliance in the study.
- •Any severe somatic illness that would interfere with compliance and participation in the study.
- •Use of high dose vitamin B3 supplementation within 30 days of enrollment.
- •Metabolic, neoplastic, or other physically or mentally debilitating disorder at baseline visit.
- •Current treatment with Oral Anti-coagulation Therapies
- •Implants that preclude MRI examinations, e.g. DBS, pacemaker
结局指标
主要结局
Cerebral NAD levels measured by 31P-MRS
时间窗: 12 weeks for primary analysis. 4, 8 and 12 weeks for secondary analysis.
Change in cerebral NAD/ATP-α ratio measured by 31 Phosphorus magnetic resonance spectroscopy (31P-MRS) in the posterior brain (encompassing the occipital, parietooccipital and posterior parts of the temporal cortex).
次要结局
- CSF NAD or other metabolite of the NAD metabolome, measured by LC-MS(12 weeks)