Effects of Orally Administered Nicotinamide Riboside on Bioenergetic Metabolism, Oxidative Stress and Cognition in Mild Cognitive Impairment and Mild Alzheimer's Dementia
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 21
- 试验地点
- 2
- 主要终点
- Changes in brain NAD+
研究概览
简要总结
The primary aim of this study is to investigate the effects of exogenously administered nicotinamide riboside (NR) on brain energy metabolism, oxidative stress, and cognitive function in individuals with mild cognitive impairment (MCI) and mild Alzheimer's dementia (AD).
详细描述
Mitochondrial function is mediated, in part, by nicotinamide adenine dinucleotide (NAD). Unfortunately, decreases in NAD+ levels are associated with normal aging, and also with numerous diseases such as AD. Accumulating evidence suggests that NR can enhance mitochondrial function and help slow or reverse these age-related abnormalities. Numerous preclinical and clinical studies have been performed using NR and related compounds to boost NAD+ level in human subjects with various diseases or animal models. However, no studies to date have investigated in vivo metabolic and bioenergetic changes (target engagement) associated with NR supplementation. In this project, we aim to investigate the neurobiological mechanisms and clinical effects of NR in patients with MCI and mild AD using in vivo novel neuroimaging techniques.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 55 Years 至 89 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Ability of the participant and/or his/her legally authorized representative to understand the purpose and risks of the study, to provide signed and dated informed consent, and to authorize the use of confidential health information.
- •Ability to speak and read fluently in English
- •55-89 years old (inclusive)
- •Normal or corrected to normal hearing and vision
- •Meet clinical diagnostic criteria for MCI or Mild AD, according to the following criteria:
- •CDR Global Score of 0.5 (MCI) or 1.0 (mild AD)
- •2018 NIA-AA guidelines for MCI/mild AD
- •Study partner available for the duration of trial participation
- •At least one copy of the APOE ε4 allele or AD+ including Amyloid positive PET scan, Tau positive PET Scan (MK6240 et al.), or CSF AD biomarkers [i.e., amyloid-beta beta (Aβ42) total (T)-tau, and phosphorylated (P)-tau]
- •An aggregate risk score > 4 according to the risk analysis method developed by Sabbagh et al. (2017)
- •For individuals who are taking niacin (or a vitamin supplement with niacin) of >200mg, the completion of a two-week wash-out period
排除标准
- •Current serious or unstable medical or neurological condition that could affect cognitive functioning, as determined by study clinician
- •Clinically unstable mood or anxiety disorder within 6 months prior to screening, as determined by study clinician
- •Lifetime history of psychotic disorder (i.e. Schizophrenia, Schizoaffective Disorder), as determined by study clinician
- •Diagnosis of a mitochondrial disorder
- •Any MRI safety contraindications
- •History of drug hypersensitivity or intolerance to NR
- •Transient ischemic attack or stroke within 1 year prior to screening
- •History of alcohol or substance abuse within prior year, as determined by study clinician and urine toxicology screen
- •History of head injury rated as moderate or worse, per DSM-5 criteria
- •History of seizure within prior 10 years
- •Current use of medication with known adverse effects on cognition (benzodiazepines, barbiturates, opiate analgesics, first generation antipsychotic medication, centrally acting anticholinergics, sedating antihistamines, tricyclic anti-depressants)
- •Change in dose of any psychiatric medications within 4 weeks of screening visit
- •Prior use of L-DOPA, any anti-Parkinsonian medication, or prior treatment with anti-amyloid immunotherapy
- •Current use of putative mitochondrial enhancers and antioxidants (e.g carnitine, creatine Co-Q10, N-acetyl cysteine [NAC], pramipexole)
- •Initiation of treatment or change in dosing of acetylcholinesterase inhibitors (AChEIs) and memantine within 4 weeks of baseline visit
- •Prior use of prescription narcotics 4 weeks before baseline visit
- •Female subjects who are pregnant or breastfeeding
- •The use of current use of niacin (or a vitamin supplement with niacin) >200mg within the last two weeks prior to study visit.
- •Current or lifetime history of cancer.
研究组 & 干预措施
Mild Cognitive Impairment and Alzheimer's Dementia
Participants will take 4 pills every day, each containing 250 mg NR (NIAGEN® by Chromadex; www.chromadex.com), via the oral route, for 12 weeks.
干预措施: Nicotinamide riboside (Drug)
结局指标
主要结局
Changes in brain NAD+
时间窗: Baseline, 6 and 12 weeks, pre- and post- 1000 mg NR daily
Changes in brain NAD+ levels
Changes in brain redox state
时间窗: Baseline, 6 and 12 weeks, pre- and post- 1000 mg NR daily
Changes in brain NAD+/NADH ratio
次要结局
- Changes in mitochondrial function(Baseline, 6 and 12 weeks, pre- and post- 1000 mg NR daily)
- Changes in antioxidant glutathione (GSH) levels(Baseline, 6 and 12 weeks, pre- and post- 1000 mg NR daily)
研究者
Fei Du
Director, Laboratory for High-Field Imaging and Translational Neuroscience
Mclean Hospital