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
| ISRCTN | ISRCTN45028842 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN45028842 |
| EudraCT/CTIS number | 2021-003345-38 |
| IRAS number | 301752 |
| Secondary identifying numbers | PID 15775, IRAS 301752, CPMS 51286 |
- Submission date
- 02/11/2021
- Registration date
- 02/12/2021
- Last edited
- 10/03/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nervous System Diseases
Plain English Summary
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
Contact information
Scientific
Nuffield Department of Clinical Neurosciences
Level 6, West Wing
John Radcliffe Hospital
Oxford
OX3 9DU
United Kingdom
 ORCID ID |
0000-0001-5490-1697 |
|---|---|
| Phone | +44 (0)1865 223380 |
| kevin.talbot@ndcn.ox.ac.uk |
Public
Nuffield Department of Clinical Neurosciences
Level 6, West Wing
John Radcliffe Hospital
Oxford
OX3 9DU
United Kingdom
| ORCID ID |
0000-0001-5651-6258 |
|---|---|
| Phone | +44 (0)1865 234829 |
| trust@ndcn.ox.ac.uk |
Scientific
Nuffield Department of Clinical Neurosciences
University of Oxford
Oxford
OX3 9DU
United Kingdom
| Phone | +44 (0)7944 184795 |
|---|---|
| elizabeth.gray@ndcn.ox.ac.uk |
Study information
| Study design | Single-centre interventional open-label non-randomized non-controlled proof of concept study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised study |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet |
| Scientific title | Terazosin RepUrposing STudy in amyotrophic lateral sclerosis: a pilot study targeting PGK1 with terazosin in ALS patients |
| Study acronym | TRUST |
| Study hypothesis | Terazosin treatment significantly affects key biomarkers of neurodegeneration in patients with amyotrophic lateral sclerosis (ALS) |
| Ethics approval(s) | Approved 21/12/2022, East Midlands – Leicester Central REC (Equinox House, City Link, Nottingham NG2 4LA, UK; +44 (0)207 104 8070; leicestercentral.rec@hra.nhs.uk),ref: 21/EM/0251 |
| Condition | Amyotrophic lateral sclerosis |
| Intervention | Total duration of intervention and follow-up is 6 months. 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. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Terazosin |
| Primary outcome measure | Plasma neurofilament light chain measured using ELISA assay at baseline and 6 months |
| Secondary outcome measures | 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) 2. Plasma biomarkers measured using ELISA assay at baseline, 3 months and 6 months (neurofilament light chain and phosphorylated neurofilament heavy chain) 3. Urine biomarker measured using ELISA assay at baseline, 3 months and 6 months (Titin N-terminal fragment) 4. Functional status measured using the Revised ALS Functional Rating Scale (ALSFRS-R) score measured at baseline, 3 months and 6 months 5. Lung strength measured using Forced Vital Capacity (FVC) at baseline, 3 months and 6 months 6. Survival (data obtained by reviewing patient notes) 7. Adverse events related to IMP and proportion of patients that drop out due to adverse events (data collected from patients) |
| Overall study start date | 02/08/2021 |
| Overall study end date | 31/03/2025 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 50 |
| Participant 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 |
| Participant 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 |
| Recruitment start date | 03/08/2022 |
| Recruitment end date | 31/05/2024 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
Headley Way
Oxford
OX3 9DU
United Kingdom
Sponsor information
University/education
RGEA, Joint Research Office
1st Floor, Boundary Brook House
Churchill Drive
Headington
Oxford
OX3 7GB
England
United Kingdom
| Phone | +44 (0)1865 289884 |
|---|---|
| ctrg@admin.ox.ac.uk | |
| Website | https://researchsupport.admin.ox.ac.uk/contacts/rgea#/ |
"ROR" |
https://ror.org/052gg0110 |
Funders
Funder type
Charity
No information available
Results and Publications
| Intention to publish date | 31/03/2026 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal |
| IPD sharing plan | The data-sharing plans for the current study are unknown and will be made available at a later date |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol file | version 2.0 | 13/12/2021 | 16/09/2022 | No | No |
| HRA research summary | 28/06/2023 | No | No |
Additional files
Editorial Notes
10/03/2025: The intention to publish date was changed from 31/03/2025 to 31/03/2026.
01/05/2024: The intention to publish date was changed from 02/08/2024 to 31/03/2025.
04/03/2024: The following changes were made to the study record:
1. The recruitment end date was changed from 31/12/2023 to 31/05/2024.
2. The overall study end date was changed from 31/03/2024 to 31/03/2025.
14/11/2023: The overall study end date was changed from 31/12/2023 to 31/03/2024.
13/07/2023: The recruitment end date was changed from 28/02/2023 to 31/12/2023.
08/02/2023: The overall trial end date was changed from 02/08/2023 to 31/12/2023 and the plain English summary was updated accordingly.
16/09/2022: Contact details updated. Uploaded protocol (not peer reviewed).
15/09/2022: The following changes were made to the trial record:
1. Ethics approval details added.
2. The recruitment start date was changed from 01/02/2022 to 03/08/2022.
3. The recruitment end date was changed from 01/10/2022 to 28/02/2023.
11/01/2022: The CPMS number was added to the protocol/serial no. field.
08/12/2021: The recruitment start date has been changed from 01/12/2021 to 01/02/2022.
08/11/2021: Internal review.
03/11/2021: Trial's existence confirmed by University of Oxford.
