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Target Engagement of Terazosin in Healthy Adults

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ClinicalTrials.gov Identifier: NCT04551040
Recruitment Status : Recruiting
First Posted : September 16, 2020
Last Update Posted : April 1, 2021
Sponsor:
Collaborator:
Michael J. Fox Foundation for Parkinson's Research
Information provided by (Responsible Party):
Jordan Schultz, University of Iowa

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.)

Condition or disease Intervention/treatment Phase
Healthy Drug: Terazosin Phase 1

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.

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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

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Primary Cohort
Titrating doses of terazosin starting at 1mg daily and increasing to 5mg daily on a weekly basis for five weeks.
Drug: Terazosin
Terazosin 1 mg oral capsule
Other Name: Hytrin




Primary Outcome Measures :
  1. 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

  2. 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)

  3. 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)

  4. 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

  5. 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)

  6. 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)

  7. 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

  8. 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)

  9. 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)

  10. 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.


Secondary Outcome Measures :
  1. Safety and Tolerability [ Time Frame: Ongoing (days 1 - 37) ]
    We will assess patient-reported adverse events.



Information from the National Library of Medicine

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Ages Eligible for Study:   60 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

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


Contacts
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Contact: Stephen Cross, BA 319-384-9391 stephen-cross@uiowa.edu
Contact: Jordan Schultz, PharmD 319-384-9388 jordan-schultz@uiowa.edu

Locations
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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         
Sponsors and Collaborators
University of Iowa
Michael J. Fox Foundation for Parkinson's Research
Investigators
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Principal Investigator: Jordan Schultz, PharmD University of Iowa
Publications:
Hytrin (terazosin) [package insert]. Abbott Indistries, North Chicago, IL. 2001.

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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.

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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
Keywords provided by Jordan Schultz, University of Iowa:
Terazosin
Hytrin
Target engagement
Glycolysis
ATP
Additional relevant MeSH terms:
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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