A Double Blind, Randomized Trial Investigating the Safety, Feasibility, and Mechanisms of Psychedelics in Healthy Older Adults With Low Well-being as Moderated by Biomarkers for Preclinical Alzheimer's Disease
概览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Acute changes in EEG-based ESBA
概览
简要总结
This study is being conducted to understand changes in brain activity following administration of two different drugs (Psilocybin and Dextromethorphan) in older adults with low well-being.
The main questions it aims to answer are, does psilocybin:
- Acutely increase complexity of EEG activity in older adults with low well-being, as modulated by the presence of biomarkers of Alzheimer's disease (AD) pathology.
- Longitudinally decrease plasma markers of neuroinflammation, as modulated by the presence of biomarkers of AD pathology.
- Explore longitudinal changes in autonomic physiology via wearable recording devices as well as longitudinal structural and functional brain changes measured in the MRI
Participants will be in the study for up to 3 months, which will include 3 to 4 in person visits and 3 to 4 remote visits. Most visits will be between 1 to 3 hours, but the dosing visit will last a minimum of 8 hours and could be as long as 12 hours. During the dosing visit, all participants will receive a single dose of the study drugs and dosages listed below.
Researchers will compare participants who receive the following drug options:
- A low-to-moderate dose of Psilocybin (5-10 mg)
- A moderate-to-high dose of Psilocybin (25-30 mg)
- A low-to-moderate dose of Dextromethorphan (30-60 mg)
- A moderate-to-high dose of Dextromethorphan (80-90 mg)
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, Outcomes Assessor)
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
- 是
入选标准
- •The eligibility criteria are deliberately incomplete to preserve the scientific integrity of the study.
- •Inclusion Criteria:
- •Are between 50-85 years inclusive at time of consent signing
- •Have below-average well-being, defined by the World Health Organization Well-Being Index (WHO-5)
- •Have no cognitive impairments, indicated by a Mini-Mental State Examination (MMSE) score \>24
- •Have an identified willing contact person with at least weekly contact with the participant to be able to provide meaningful information about the participant's daily function and able to pick up the study participant at the end of the Dosing Visit
- •Participants assigned female sex at birth must be non-lactating, and post-menopausal, defined as a period of over 12 months since the last menstrual period, or otherwise physically unable to become pregnant
- •Participants assigned male sex at birth must 1) refrain from sperm donation for 3 months after the Dosing Visit, and 2) if engaging in sexual activities that may result in pregnancy, must use a condom, plus their partner of childbearing potential must use a second, highly effective form of contraception for 3 months after the Dosing Visit
- •Be proficient in English
- •Are able and willing to provide consent as assessed by comprehension questions in informed consent process
排除标准
- •Have a known allergic or severe reaction to Psilocybin, Dextromethorphan, or any of the non-active components of the IMP capsules
- •Insufficient ability to report on symptoms to make a valid assessment on any required instrument
- •Have a condition or presence of clinical feature which, in the opinion of the investigators might interfere with or prevent appropriate study participation or interfere with data interpretation
- •MRI Exclusions:
- •Any implanted object or device that poses a safety risk or could interfere with MRI scanning (e.g. aneurysm clips, cardiac pacemakers, defibrillators, neurostimulators, cochlear implants, spinal cord stimulators, insulin or infusion pumps, metallic prostheses or fragments, heart valves, vascular stents, or shunts. surgical staples, clips, or joint replacements, radiation seeds, medication patches containing metal, or any other metallic or electronic implants)
- •History of metallic injury to the eyes or body, or those with tattoos containing metallic ink, permanent makeup, or body piercings that cannot be removed.
- •Any condition that poses a safety risk or could interfere with MRI scanning (e.g. severe claustrophobia or motion disorders or breathing problems, etc)
- •Psychiatric:
- •History of hallucinogen persisting perception disorder (HPPD) (as per DSM-5 criteria)
- •Cardiovascular:
研究组 & 干预措施
A low-to-moderate dose of Dextromethorphan (30-60 mg)
A single low-to-moderate dose of Dextromethorphan (30-60 mg)
干预措施: Dextromethorphan (DXM) (Drug)
A moderate-to-high dose of Dextromethorphan (80-90 mg)
A single moderate-to-high dose of Dextromethorphan (80-90 mg)
干预措施: Dextromethorphan (DXM) (Drug)
A low-to-moderate dose of Psilocybin (5-10 mg)
A single low-to-moderate dose of Psilocybin (5-10 mg)
干预措施: Psilocybin (drug) (Drug)
A moderate-to-high dose of Psilocybin (25-30 mg)
A single moderate-to-high dose of Psilocybin (25-30 mg)
干预措施: Psilocybin (drug) (Drug)
结局指标
主要结局
Acute changes in EEG-based ESBA
时间窗: Pre- to post-dose two hours later
Compare acute changes in EEG-based Lempel Ziv complexity (pre- to post-dose, arbitrary unit) between the four study arms, with the presence of biomarkers of AD pathology used in the statistical analyses as a moderator. Lempel-Ziv complexity in EEG is a non-linear analysis tool that quantifies the amount of entropy of spontaneous brain activity (ESBA).
次要结局
- Changes in TNF-alpha(Screening to three weeks post dosing)
研究者
Jennifer Mitchell
Professor
University of California, San Francisco