Assessing Target Engagement of Terazosin in Healthy Adults
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Change in glycolysis in the brain from baseline to 1 week (1mg of terazosin)
研究概览
简要总结
The purpose of the study is to assess the target engagement of Terazosin (TZ) in a single cohort of 6 healthy adult participants. During the study participants will undergo PET/CT scans, 7-Tesla MRI scans, blood draws, and an optional lumbar puncture (LP.)
详细描述
The study is a single center, 37-day, controlled pilot study to assess the target engagement of Terazosin (TZ) in a single cohort of 6 healthy adult participants (3 men and 3 women.) During the study participants will undergo PET/CT scans, 7-Tesla MRI scans, blood draws, and an optional lumbar puncture (LP.) Participants will have their baseline ATP levels measured (at 0mg TZ.) They will then take doses of TZ at 1mg and will increase their dose on a weekly basis by 1mg until they reach a total dose of 5mg. ATP levels will be assessed on study days 8 and 36. Participants interested in voluntarily donating a sample of cerebral spinal fluid will undergo an optional lumbar puncture on study day 37.
The purpose of the study is to gain a better understanding of the mechanisms in which TZ acts in the brain. TZ was recently discovered to increase energy levels (in the form of ATP molecules) in the brain by enhancing glycolysis. By using different brain imaging techniques, blood assays and cerebral spinal fluid assays, the study will attempt to: 1) quantify the rate of glycolysis in the brain at different dosages of TZ, 2) quantify ATP levels in the brain at different dosages of TZ, 3) quantify ATP levels in blood at different dosages of TZ, and 4) assess the brain permeability of TZ. It is hoped that knowledge gained from the study will help guide future clinical trials using TZ for the treatment of various neurodegenerative diseases such as Parkinson's Disease.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 60 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy Men or women aged 60-90
排除标准
- •History of stroke
- •Ineligibility for MRI (e.g. soft tissue metallic implants, clips, cardiac pacemaker, cardiac defibrillator, internal pacing wires, metallic fragments, shrapnel, etc.)
- •Current use of more than one of the following classes of medications: beta blockers, ace inhibitors, angiotensin receptor blockers, calcium channel blockers, or diuretics
- •Use of any alpha blockers (terazosin, doxazosin, alfuzosin, prazosin, or tamsulosin) in the past year.
- •Current use of the over-the-counter supplement yohimbe
- •Orthostatic hypotension defined as symptomatic decrease in BP > 20mmHg systolic or > 10mmHg diastolic and HR increase < 20bpm on supine to sitting or standing.
- •Alcohol and drug abuse
- •Clinically significant traumatic brain injury
- •History of Type I diabetes
- •Uncontrolled Type II diabetes
- •Other known medical or psychiatric comorbidity that in the investigator's opinion would compromise participation in the study or increase fall risk
- •Use of investigational drugs within 30 days before screening
- •History of hemodynamic instability
- •For females: pregnancy or breastfeeding
研究组 & 干预措施
Primary Cohort
Titrating doses of terazosin starting at 1mg daily and increasing to 5mg daily on a weekly basis for five weeks.
干预措施: Terazosin (Drug)
结局指标
主要结局
Change in glycolysis in the brain from baseline to 1 week (1mg of terazosin)
时间窗: Study day 8
Use of FDG PET to determine how TZ quantitatively increases glycolysis as measured by FDG uptake from baseline to 1 week (Day 8/ 1mg TZ)
Quantification of TZ in Cerebrospinal Fluid
时间窗: Study day 37
Participants will be given the option to undergo a lumbar puncture on Day 37 (5 mg TZ). Their blood will also be drawn to compare levels of TZ in the blood to levels detected in the CSF.
Quantification of ATP in brain at baseline
时间窗: Study day 1
Use of Magnetic Resonance Spectroscopy (MRS) to quantify ATP in the brain at baseline prior to initiation of terazosin
Quantification of glycolysis in the brain at baseline
时间窗: Study day 1
Use of FDG PET to quantify glycolysis in the brain at baseline prior to initiation of terazosin
Change in ATP in the brain from baseline to 5 weeks (5mg of terazosin)
时间窗: Study day 36
Use of Magnetic Resonance Spectroscopy (MRS) determine how TZ quantitatively increases ATP as measured by MRS from baseline to 5 weeks (Day 36/ 5mg TZ)
Change in ATP in the blood from baseline to 5 week (1mg of terazosin)
时间窗: Study day 36
Use of a novel assay to determine how TZ quantitatively increases ATP in the blood from baseline to 5 weeks (Day 36/ 5mg TZ)
Change in ATP in the brain from baseline to 1 week (1mg of terazosin)
时间窗: Study day 8
Use of Magnetic Resonance Spectroscopy (MRS) determine how TZ quantitatively increases ATP as measured by MRS from baseline to 1 week (Day 8/ 1mg TZ)
Change in glycolysis in the brain from baseline to 5 weeks (5mg of terazosin)
时间窗: Study day 36
Use of FDG PET to determine how TZ quantitatively increases glycolysis as measured by FDG uptake from baseline to 5 weeks (Day 36/ 5mg TZ)
Quantification of ATP in blood at baseline
时间窗: Study day 1
Use of a novel assay to quantify ATP in the blood at baseline prior to initiation of terazosin
Change in ATP in the blood from baseline to 1 week (1mg of terazosin)
时间窗: Study day 8
Use of a novel assay to determine how TZ quantitatively increases ATP in the blood from baseline to 1 week (Day 8/ 1mg TZ)
次要结局
- Safety and Tolerability(Ongoing (days 1 - 37))
研究者
Jordan Schultz
Assistant Professor
University of Iowa