Effect of Terazosin on ATP Levels in People With Amyotrophic Lateral Sclerosis (TZ-ALS)

University of Iowa

Status and phase

Enrolling

Early Phase 1

Conditions

Adenosine Triphosphate Activities

Amyotrophic Lateral Sclerosis

Treatments

Drug: Terazosine

Study type

Interventional

Funder types

Other

Identifiers

NCT07224269

202408197

Details and patient eligibility

About

This will be a single center, open label pilot study to assess the safety and tolerability of terazosin (TZ) at a dose of 5 milligrams (mg) per os (PO) daily for patients with amyotrophic lateral sclerosis (ALS). The primary outcome of this study is to determine whether TZ increases adenosine triphosphate (ATP) levels in ALS. The investigators will measure adverse outcomes, safety, and tolerability of taking TZ. Procedures include blood draws, spirometry, lumbar punctures, fluorodeoxyglucose-positron emission tomography (FDG-PET) scans, questionnaires, and physical examinations. TZ will be titrated up to 5 mg PO daily. This is a pilot study and is not powered to assess efficacy of this medication. The investigators' hope is that this study will guide future studies of this (and similar) medications for the disease modification of ALS. This study also aims to learn more about how patients produce and use energy and if TZ can help to reverse energy deficits that appear in ALS.

Enrollment

15 estimated patients

Sex

All

Ages

18 to 80 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

INCLUSION CRITERIA

Ages 18 - 80 years old
Diagnosed with ALS based on Gold Coast Criteria
ALS symptom onset within 36 months at enrollment
Slow vital capacity (SVC) > 65%
Riluzole use-Never taken or taking a stable dose for at least 4 weeks prior to screening visit or will refrain from starting for the duration of the study
Edaravone use-Never taken or completed at least one cycle (typically 14 days) prior to screening visit or will refrain from starting for the duration of the study
Must have the ability to swallow pills at the time of the screening visit, and in the principle investigator's opinion, have the ability to swallow pills for the duration of the study
Willing to use highly effective contraception for the duration of the trial treatment and for a duration of 80 days after the last dose.

EXCLUSION CRITERIA

Orthostatic hypotension at screening is defined as decrease in BP > 20 mmHg systolic or > 10 mmHg diastolic and HR increase <20 bpm on transition from supine to sitting or from sitting to standing
Known allergy or previous adverse reaction to terazosin or related compound
Current use of terazosin or concurrent use of doxazosin, alfuzosin, prazosin, or tamsulosin at the time of screening visit or within the 3 months prior to baseline visit
Current diagnosis or healthcare professional-recommended treatment (medication, exercise or diet) of diabetes mellitus (type 1 or type 2)
Screening glucose >140 mg/dl
Pregnancy or breastfeeding women
Taking therapeutic anticoagulant medication (i.e. warfarin, DOAC's, full dose Lovenox or heparin)
Liver function blood tests (ALT or AST) more than twice the upper limit of normal
Hemoglobin < 11.0 g/dL
Traumatic brain injury or post-traumatic stress disorder
Presence of a confounding acute or unstable medical, psychiatric, or orthopedic condition
Noncompliant or sporadic use of medications that modulate the central nervous system
Uncontrolled major depression or bipolar affective disorder, or other mental health disorders that are, in the opinion of the PI, sufficiently severe to increase risk of experiencing an Adverse Drug Reaction (ADR)
Current suicidal ideation as measured by question 2 of the Columbia-Suicide Severity Rating Scale (C-SSRS)
Participants with insufficient decisional capacity to provide written informed consent determined by the primary investigator.
Noncompliant or sporadic use of antihypertensive medications
Unable to lie supine and still for 60 minutes for the duration of the study
Contraindications to undergoing lumbar puncture
Currently taking part in another clinical trial with an investigational medicinal product or having taken part in one in the three months prior to screening visit
Current diagnosis of diabetes (type 1 or type 2) or healthcare professional-recommended treatment (medication, exercise or diet) of diabetes mellitus
Screening visit glucose >140 mg/dl