Amiloride Clinical Trial in Optic Neuritis

ISRCTN	ISRCTN99153976
DOI	https://doi.org/10.1186/ISRCTN99153976
ClinicalTrials.gov (NCT)	NCT01802489
Clinical Trials Information System (CTIS)	2012-004980-39
Protocol serial number	13895
Sponsor	University of Oxford (UK)
Funder	Multiple Sclerosis Society (of Great Britain & Northern Ireland); Grant Codes: 952/11

Submission date: 03/05/2013
Registration date: 03/05/2013
Last edited: 06/01/2017

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Eye Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Matthew Craner
Scientific

Dept of Clinical Neurology
Level 6
West wing
Headley Way
Headington
Oxford
OX3 9DU
United Kingdom

Phone	+44 1865 222351
Email	matthew.craner@ndcn.ox.ac.uk

Study information

Primary study design	Interventional
Study design	Randomised interventional treatment trial
Secondary study design	Randomised controlled trial
Scientific title	Amiloride Clinical Trial in Optic Neuritis
Study acronym	ACTION
Study objectives	The aim of this study is to investigate the neuroprotective efficacy of amiloride in the treatment of multiple sclerosis (MS).
Ethics approval(s)	21/01/2013, ref: 13/SC/0022
Health condition(s) or problem(s) studied	Topic: Eye, Neurological; Subtopic: Eye (all Subtopics), Neurological (all Subtopics); Disease: Ophthalmology, Nervous system disorders
Intervention	Amiloride, 10mg per day active group with a double blind randomised placebo group. Study Entry : Single Randomisation only
Intervention type	Drug
Phase	Phase II
Drug / device / biological / vaccine name(s)	Amiloride
Primary outcome measure(s)	Scanning Laser Polarimetry determined retinal fibre layer thickness measured at baseline, 6 and 12 months.
Key secondary outcome measure(s)	1. Colour Vision measured at baseline, and 6 months 2. Non-conventional surrogate marker of white matter and grey matter injury and connectivity by 3T MRI measured at baseline, 6 and 12 months 3. Optical Coherence Tomography - determined difference in retinal nerve fibre layer thickness measured at baseline, 6 and 12 months 4. Quality of Life Questionnaires measured at baseline, 6 and 12 months 5. Visual Electrophysiology measured at baseline and 6 months 6. Visual Fuction measured at baselne, 6 and 12 months
Completion date	31/03/2015

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	46
Key inclusion criteria	1. Patients with a first episode of unilateral ON 2. Participants with an existing diagnosis of relapsing remitting MS and new onset of ON are eligible if they have not had a previous episode of ON 3. A duration of disease of ≤ 10 years 4. An EDSS (Expanded Disability Status Scale) of ≤3 5. No immune modulating treatment other than β-Interferon or Glatiramer Acetate at time of recruitment 6. Able to be randomised within 28 days of onset of visual symptoms 7. Visual acuity of ≤6/9 8. Participant is willing and able to give informed consent for participation in the study and able to comply with study visits 9. Male or Female, aged between 18 55 years. 10. Stable dose of current regular medication for at least 4 weeks prior to study entry 11. Female participants of child bearing potential must be willing to use two effective methods of contraception (barrier methods, hormonal methods or abstinence) during the initial 5 month treatment period of the study and for one month thereafter. 12. Participant has clinically acceptable urea and electrolytes and estimated glomerular filtration rate (eGFR) >60 13. Able and willing to comply with all study requirements. 14. Willing to allow his or her General Practitioner to be notified of participation in the study.
Key exclusion criteria	1. Previous diagnosis of ON 2. Any concomitant immune suppressing or immune modulating therapy excluding β-interferon or glatiramer acetate. 3. Female participants who are pregnant, lactating or planning pregnancy during the course of the study. 4. Concomitant potassium supplements, angiotensin converting enzyme inhibitors, angiotensin II antagonists, cyclosporine, tacrolimus or lithium 5. Any contra-indication to MRI severe claustrophobia, metal implant, pacemaker, etc. 6. Participant who is terminally ill or is inappropriate for placebo medication 7. Impaired renal function : eGFR ≤60, anuria, acute or chronic renal insufficiency and evidence of diabetic nephropathy 8. Raised serum potassium (K+ >5.5mmol/l) 9. Diabetes 10. Significant concomitant eye disease in either eye that may affect diseased or fellow eye results. 11. Any other significant disease or disorder which, in the opinion of the investigator, may either put the participants at risk because of participation in the study, or may influence the result of the study, or the participants ability to participate in the study. 12. Participants who have participated in another research study involving an investigational product in the past 12 weeks.
Date of first enrolment	19/03/2013
Date of final enrolment	31/03/2015

Locations

Countries of recruitment

United Kingdom
England

Study participating centre

Dept of Clinical Neurology

Oxford
OX3 9DU
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	09/11/2015		Yes	No
HRA research summary			28/06/2023	No	No

Editorial Notes

05/01/2017: Publication reference added.