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

Not Applicable

Conditions: Amyotrophic lateral sclerosis
Nervous System Diseases
Motor neuron disease

Registration Number: ISRCTN45028842

Lead Sponsor: niversity of Oxford

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Ongoing

Sex: All

Target Recruitment: 50

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

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Plasma neurofilament light chain measured using ELISA assay at baseline and 6 months

Secondary Outcome Measures

Name	Time	Method
1. CSF biomarkers measured using ELISA assay at baseline, 3 months and 6 months (neurofilament light chain, phosphorylated neurofilament heavy chain, chitotriosidase 1, chitinase 3-like protein 1, chitinase 3-like protein 2 and PGK1)<br>2. Plasma biomarkers measured using ELISA assay at baseline, 3 months and 6 months (neurofilament light chain and phosphorylated neurofilament heavy chain)<br>3. Urine biomarker measured using ELISA assay at baseline, 3 months and 6 months (Titin N-terminal fragment)<br>4. Functional status measured using the Revised ALS Functional Rating Scale (ALSFRS-R) score measured at baseline, 3 months and 6 months<br>5. Lung strength measured using Forced Vital Capacity (FVC) at baseline, 3 months and 6 months<br>6. Survival (data obtained by reviewing patient notes)<br>7. Adverse events related to IMP and proportion of patients that drop out due to adverse events (data collected from patients)