Clinical trial NCT04551040: Target Engagement of Terazosin in Healthy Adults
Official title: Assessing Target Engagement of Terazosin in Healthy Adults
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Healthy
Keywords: Terazosin
Hytrin
Target engagement
Glycolysis
ATP
Lead sponsor: University of Iowa
Sponsor class: OTHER
Collaborators: name: Michael J. Fox Foundation for Parkinson's Research
First posted: 2020-09-16
Enrollment: 18
Sex: ALL
Minimum age (years): 60
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single group of healthy older adults
Primary purpose: OTHER

Brief summary: 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.)

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Healthy Men or women aged 60-90

Exclusion Criteria:

* 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

Primary outcomes:
measure: Quantification of glycolysis in the brain at baseline
timeFrame: Study day 1
measure: Change in glycolysis in the brain from baseline to 1 week (1mg of terazosin)
timeFrame: Study day 8
measure: Change in glycolysis in the brain from baseline to 5 weeks (5mg of terazosin)
timeFrame: Study day 36
measure: Quantification of ATP in brain at baseline
timeFrame: Study day 1
measure: Change in ATP in the brain from baseline to 1 week (1mg of terazosin)
timeFrame: Study day 8
measure: Change in ATP in the brain from baseline to 5 weeks (5mg of terazosin)
timeFrame: Study day 36
measure: Quantification of ATP in blood at baseline
timeFrame: Study day 1
measure: Change in ATP in the blood from baseline to 1 week (1mg of terazosin)
timeFrame: Study day 8
measure: Change in ATP in the blood from baseline to 5 week (1mg of terazosin)
timeFrame: Study day 36
measure: Quantification of TZ in Cerebrospinal Fluid
timeFrame: Study day 37
Secondary outcomes:
measure: Safety and Tolerability
timeFrame: Ongoing (days 1 - 37)
Other outcomes:
Locations:
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
Study officials:
affiliation: University of Iowa
name: Jordan Schultz, PharmD
role: PRINCIPAL_INVESTIGATOR
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