Target Engagement of Terazosin in Healthy Adults
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| ClinicalTrials.gov Identifier: NCT04551040 |
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Recruitment Status :
Recruiting
First Posted : September 16, 2020
Last Update Posted : April 1, 2021
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Healthy | Drug: Terazosin | Phase 1 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 6 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Intervention Model Description: | Single group of healthy older adults |
| Masking: | None (Open Label) |
| Primary Purpose: | Other |
| Official Title: | Assessing Target Engagement of Terazosin in Healthy Adults |
| Actual Study Start Date : | March 26, 2021 |
| Estimated Primary Completion Date : | November 1, 2021 |
| Estimated Study Completion Date : | November 1, 2021 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Primary Cohort
Titrating doses of terazosin starting at 1mg daily and increasing to 5mg daily on a weekly basis for five weeks.
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Drug: Terazosin
Terazosin 1 mg oral capsule
Other Name: Hytrin |
- Quantification of glycolysis in the brain at baseline [ Time Frame: Study day 1 ]Use of FDG PET to quantify glycolysis in the brain at baseline prior to initiation of terazosin
- Change in glycolysis in the brain from baseline to 1 week (1mg of terazosin) [ Time Frame: 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)
- Change in glycolysis in the brain from baseline to 5 weeks (5mg of terazosin) [ Time Frame: 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 brain at baseline [ Time Frame: Study day 1 ]Use of Magnetic Resonance Spectroscopy (MRS) to quantify ATP in the brain at baseline prior to initiation of terazosin
- Change in ATP in the brain from baseline to 1 week (1mg of terazosin) [ Time Frame: 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 ATP in the brain from baseline to 5 weeks (5mg of terazosin) [ Time Frame: 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)
- Quantification of ATP in blood at baseline [ Time Frame: 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) [ Time Frame: 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)
- Change in ATP in the blood from baseline to 5 week (1mg of terazosin) [ Time Frame: 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)
- Quantification of TZ in Cerebrospinal Fluid [ Time Frame: 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.
- Safety and Tolerability [ Time Frame: Ongoing (days 1 - 37) ]We will assess patient-reported adverse events.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 60 Years to 90 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | Yes |
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04551040
| Contact: Stephen Cross, BA | 319-384-9391 | stephen-cross@uiowa.edu | |
| Contact: Jordan Schultz, PharmD | 319-384-9388 | jordan-schultz@uiowa.edu |
| United States, Iowa | |
| University of Iowa Hospitals and Clinics | Recruiting |
| Iowa City, Iowa, United States, 52242 | |
| Contact: Stephen Cross, BA 319-384-9391 stephen-cross@uiowa.edu | |
| Contact: Jordan Schultz, PharmD 319-384-9388 jordan-schultz@uiowa.edu | |
| Principal Investigator: Jordan Schultz, PharmD | |
| Sub-Investigator: Nandakumar Narayanan, MD, PhD | |
| Principal Investigator: | Jordan Schultz, PharmD | University of Iowa |
| Responsible Party: | Jordan Schultz, Assistant Professor, University of Iowa |
| ClinicalTrials.gov Identifier: | NCT04551040 |
| Other Study ID Numbers: |
202005461 |
| First Posted: | September 16, 2020 Key Record Dates |
| Last Update Posted: | April 1, 2021 |
| Last Verified: | March 2021 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | The Michael J. Fox Foundation for Parkinson's Research requires all funded investigators to share data with the foundation. The Foundation will make de-identified, patient-specific data available to interested investigators upon reasonable request. |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
| Product Manufactured in and Exported from the U.S.: | No |
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Terazosin Hytrin Target engagement Glycolysis ATP |
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Terazosin Adrenergic alpha-1 Receptor Antagonists Adrenergic alpha-Antagonists Adrenergic Antagonists Adrenergic Agents |
Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Physiological Effects of Drugs Urological Agents |