A pilot trial to test whether terazosin treatment lowers the levels of biomarkers of neurodegeneration (nerve cell damage) in the blood, spinal fluid, and urine of amyotrophic lateral sclerosis patients over 6 months

Trial ID: ISRCTN45028842

Other - Phase Unknown - No longer available

Background and study aims Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND), is a neurodegenerative disease in which motor neurons deteriorate leading to progressive weakness. Treatment options are very limited. Laboratory evidence suggests that an enzyme called phosphoglycerate kinase 1 (PGK1) might help to protect motor neurons by increasing their energy availability. The drug terazosin is known to activate PGK1, and researchers at the University of Oxford and University of Edinburgh have shown that terazosin helps motor neuron survival in laboratory models of the disease. Terazosin is a drug that is routinely prescribed to patients either for high blood pressure or for symptoms arising from an enlarged prostate gland in men, where it acts through a different mechanism from PGK1 activation. As motor neurons deteriorate in ALS, they release substances that can be measured in body fluids and give an indication of how active the disease is. These are called biomarkers. In this pilot study, we will test whether terazosin treatment significantly lowers the levels of biomarkers in the blood, spinal fluid and urine at intervals over the course of 6 months. We will also monitor clinical measurements of disease progression, such as the ALS Functional Rating Score and the spirometry ‘breathing’ test, which are carried out as part of your routine clinical appointments. If this study shows that terazosin alters biomarker levels, suggesting that it potentially slows the disease process in patients with ALS, it would then make a strong case for a larger-scale clinical trial. Who can participate? Adults over 18 years, diagnosed with ALS and first onset of symptoms between 9 - 24 months ago. What does the study involve? Participants will take up to 10mg oral terazosin daily for up to 6 months. There will be 3 face-to-face study visits (at baseline, 3 months and 6 months), involving the following procedures: ALSFRS-R questionnaire, spirometry test, blood samples, lumbar puncture, urine sample, blood pressure measurement. What are the possible benefits and risks of participating? There are potential risks associated with the blood sampling and lumbar puncture, plus the side effects of the drug (how much detail do you need?). No guaranteed direct benefit to participants, however, we hope that the results of this study will help to inform future research into treatments for ALS. Where is the study run from? University of Oxford (UK) When is the study starting and how long is it expected to run for? August 2021 to March 2025 Who is funding the study? My Name’5 Doddie Foundation (UK) Who is the main contact? Prof. Kevin Talbot, kevin.talbot@ndcn.ox.ac.uk Emma Harper, trust@ndcn.ox.ac.uk

Conditions

• Amyotrophic lateral sclerosis
• Nervous System Diseases
• Motor neuron disease

Interventions

• Terazosin

Eligibility

Inclusion criteria

• 1. Participant is willing and able to give informed consent for participation in the study 2. Male or female, aged 18 years or above 3. Diagnosed with ALS (Gold Coast Criteria) 4. Symptom onset (first weakness) 9-24 months (inclusive) at enrolment 5. Taking riluzole at a stable dose for at least 4 weeks prior to enrolment, or will refrain from starting riluzole for the duration of the study, or have never taken riluzole 6. Able to swallow tablets safely 7. Willing to use highly effective contraception for the duration of trial treatment and for a duration of 80 days after the last dose

Exclusion criteria

• 1. Using non-invasive ventilation (NIV) 2. Pregnancy 3. Any other significant disease, disorder, or finding which may significantly increase the risk to the volunteer because of participation in the study, affect the ability of the volunteer to participate in the study or impair interpretation of the study data 4. Hypersensitivity to the IMP or any of its excipients (including lactose) 5. Taking terazosin or other alpha adrenergic blockers (doxazosin, prazosin, tamsulosin, silodosin, trazodone, tolazoline, phentolamine, phenoxybenzamine) at time of screening visit or within the 3 months prior to baseline visit 6. Ongoing use of sildenafil, tadalafil, or vardenafil 7. Taking anti-coagulant medication, e.g. warfarin or apixaban 8. Symptomatic postural hypotension or history of postural hypotension 9. Systemic hypotension (systolic BP ≤90mmHg or diastolic BP≤60mmHg) 10. History of micturition syncope 11. Contraindications to lumbar puncture 12. Taking part in a current CTIMP or have taken part in any CTIMP in the 3 months prior to recruitment

Sponsor

University of Oxford

Source: https://www.isrctn.com/

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