Target Engagement of Terazosin in Healthy Adults

NCT04551040 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 202005461
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.)

Conditions

Healthy

Keywords

Terazosin; Hytrin; Target engagement; Glycolysis; ATP

Outcome Measures

Primary Outcomes (10)

• Quantification of glycolysis in the brain at baseline

  Use of FDG PET to quantify glycolysis in the brain at baseline prior to initiation of terazosin

  Study day 1

• Change in glycolysis in the brain from baseline to 1 week (1mg of terazosin)

  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)

  Study day 8

• Change in glycolysis in the brain from baseline to 5 weeks (5mg of terazosin)

  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)

  Study day 36

• Quantification of ATP in brain at baseline

  Use of Magnetic Resonance Spectroscopy (MRS) to quantify ATP in the brain at baseline prior to initiation of terazosin

  Study day 1

• Change in ATP in the brain from baseline to 1 week (1mg of terazosin)

  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)

  Study day 8

• Change in ATP in the brain from baseline to 5 weeks (5mg of terazosin)

  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)

  Study day 36

• Quantification of ATP in blood at baseline

  Use of a novel assay to quantify ATP in the blood at baseline prior to initiation of terazosin

  Study day 1

• Change in ATP in the blood from baseline to 1 week (1mg of terazosin)

  Use of a novel assay to determine how TZ quantitatively increases ATP in the blood from baseline to 1 week (Day 8/ 1mg TZ)

  Study day 8

• Change in ATP in the blood from baseline to 5 week (1mg of terazosin)

  Use of a novel assay to determine how TZ quantitatively increases ATP in the blood from baseline to 5 weeks (Day 36/ 5mg TZ)

  Study day 36

• Quantification of TZ in Cerebrospinal Fluid

  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.

  Study day 37

Secondary Outcomes (1)

• Safety and Tolerability

  Ongoing (days 1 - 37)

Study Arms (1)

Primary Cohort

EXPERIMENTAL

Titrating doses of terazosin starting at 1mg daily and increasing to 5mg daily on a weekly basis for five weeks.

Drug: Terazosin

Interventions

Terazosin DRUG

Terazosin 1 mg oral capsule

Also known as: Hytrin

Primary Cohort

Eligibility Criteria

• Age: 60 Years - 90 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy Men or women aged 60-90

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Iowa: lead
• Michael J. Fox Foundation for Parkinson's Research: collaborator

Study Sites (1)

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

Related Publications (13)

• Chen X, Zhao C, Li X, Wang T, Li Y, Cao C, Ding Y, Dong M, Finci L, Wang JH, Li X, Liu L. Terazosin activates Pgk1 and Hsp90 to promote stress resistance. Nat Chem Biol. 2015 Jan;11(1):19-25. doi: 10.1038/nchembio.1657. Epub 2014 Nov 10.

  PMID: 25383758 BACKGROUND

• Cai R, Zhang Y, Simmering JE, Schultz JL, Li Y, Fernandez-Carasa I, Consiglio A, Raya A, Polgreen PM, Narayanan NS, Yuan Y, Chen Z, Su W, Han Y, Zhao C, Gao L, Ji X, Welsh MJ, Liu L. Enhancing glycolysis attenuates Parkinson's disease progression in models and clinical databases. J Clin Invest. 2019 Oct 1;129(10):4539-4549. doi: 10.1172/JCI129987.

  PMID: 31524631 BACKGROUND

• Schapira AH. Mitochondria in the aetiology and pathogenesis of Parkinson's disease. Lancet Neurol. 2008 Jan;7(1):97-109. doi: 10.1016/S1474-4422(07)70327-7.

  PMID: 18093566 BACKGROUND

• Hoyer S. Brain glucose and energy metabolism during normal aging. Aging (Milano). 1990 Sep;2(3):245-58. doi: 10.1007/BF03323925.

  PMID: 1982730 BACKGROUND

• Cunnane S, Nugent S, Roy M, Courchesne-Loyer A, Croteau E, Tremblay S, Castellano A, Pifferi F, Bocti C, Paquet N, Begdouri H, Bentourkia M, Turcotte E, Allard M, Barberger-Gateau P, Fulop T, Rapoport SI. Brain fuel metabolism, aging, and Alzheimer's disease. Nutrition. 2011 Jan;27(1):3-20. doi: 10.1016/j.nut.2010.07.021. Epub 2010 Oct 29.

  PMID: 21035308 BACKGROUND

• Blesa J, Phani S, Jackson-Lewis V, Przedborski S. Classic and new animal models of Parkinson's disease. J Biomed Biotechnol. 2012;2012:845618. doi: 10.1155/2012/845618. Epub 2012 Mar 28.

  PMID: 22536024 BACKGROUND

• Hoffe B, Holahan MR. The Use of Pigs as a Translational Model for Studying Neurodegenerative Diseases. Front Physiol. 2019 Jul 10;10:838. doi: 10.3389/fphys.2019.00838. eCollection 2019.

  PMID: 31354509 BACKGROUND

• Hoegger MJ, Fischer AJ, McMenimen JD, Ostedgaard LS, Tucker AJ, Awadalla MA, Moninger TO, Michalski AS, Hoffman EA, Zabner J, Stoltz DA, Welsh MJ. Impaired mucus detachment disrupts mucociliary transport in a piglet model of cystic fibrosis. Science. 2014 Aug 15;345(6198):818-22. doi: 10.1126/science.1255825.

  PMID: 25124441 BACKGROUND

• Rogers CS, Stoltz DA, Meyerholz DK, Ostedgaard LS, Rokhlina T, Taft PJ, Rogan MP, Pezzulo AA, Karp PH, Itani OA, Kabel AC, Wohlford-Lenane CL, Davis GJ, Hanfland RA, Smith TL, Samuel M, Wax D, Murphy CN, Rieke A, Whitworth K, Uc A, Starner TD, Brogden KA, Shilyansky J, McCray PB Jr, Zabner J, Prather RS, Welsh MJ. Disruption of the CFTR gene produces a model of cystic fibrosis in newborn pigs. Science. 2008 Sep 26;321(5897):1837-41. doi: 10.1126/science.1163600.

  PMID: 18818360 BACKGROUND

• Hytrin (terazosin) [package insert]. Abbott Indistries, North Chicago, IL. 2001.

  BACKGROUND

• Matthews DC, Lerman H, Lukic A, Andrews RD, Mirelman A, Wernick MN, Giladi N, Strother SC, Evans KC, Cedarbaum JM, Even-Sapir E. FDG PET Parkinson's disease-related pattern as a biomarker for clinical trials in early stage disease. Neuroimage Clin. 2018 Aug 10;20:572-579. doi: 10.1016/j.nicl.2018.08.006. eCollection 2018.

  PMID: 30186761 BACKGROUND

• Patel A, Malinovska L, Saha S, Wang J, Alberti S, Krishnan Y, Hyman AA. ATP as a biological hydrotrope. Science. 2017 May 19;356(6339):753-756. doi: 10.1126/science.aaf6846.

  PMID: 28522535 BACKGROUND

• Nair AB, Jacob S. A simple practice guide for dose conversion between animals and human. J Basic Clin Pharm. 2016 Mar;7(2):27-31. doi: 10.4103/0976-0105.177703.

  PMID: 27057123 BACKGROUND

MeSH Terms

Interventions

Terazosin

Study Officials

• Jordan Schultz, PharmD

  University of Iowa

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: Single group of healthy older adults

Study Record Dates

• First Submitted: September 9, 2020
• First Posted: September 16, 2020
• Study Start: March 26, 2021
• Primary Completion: March 1, 2023
• Study Completion: June 30, 2025
• Last Updated: January 14, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share

Locations

US (1)