Amiloride Clinical Trial In Optic Neuritis

NCT01802489 | Completed Phase 2 DMC

• 1 other identifier: Amiloride 02
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

Optic neuritis (ON) is a common event in Multiple Sclerosis (MS), and causes significant loss of nerve cells in the eye, resulting in poor vision. Optic neuritis also provides a sensitive way of testing the effectiveness of drugs that may help protect from loss of nerve cells in ON and therefore in MS. The investigators have identified through laboratory and early clinical research in humans that amiloride (a water tablet already in use) may be a drug that can be of benefit in optic neuritis by protecting from loss of nerves cells, ie a neuroprotective drug. The purpose of this study is to assess the efficacy of amiloride as a neuroprotective drug in optic neuritis

Conditions

Optic Neuritis; Multiple Sclerosis

Keywords

Optic neuritis; Multiple sclerosis; Retinal nerve fibre layer; Axonal loss; Neuroprotection; MRI; Optical coherence tomography; Amiloride; Acid Sensing Ion Channels

Outcome Measures

Primary Outcomes (1)

• Scanning laser polarimetry determined retinal nerve fibre layer thickness

  The primary outcome will be difference in retinal nerve fibre thickness at 6 months between affected eye and non-affected fellow eye at baseline between the amiloride and placebo group. An additional measure will be made at 12 months

  Baseline, 6 and 12 months

Secondary Outcomes (5)

• Optical coherence tomography determined difference in retinal nerve fibre layer thickness.

  Baseline, 6 and 12 months

• Differences between the amiloride and placebo groups in non-conventional MRI surrogate marker of white matter and grey matter injury and connectivity by 3T scanning.

  Baseline, 6 and 12 months

• Visual Function

  Baseline, 6 and 12 months

• Visual Electrophysiology

  0 and 6 months

• Quality of life questionnaires

  Baseline, 6 and 12 months

Study Arms (2)

Amiloride

ACTIVE COMPARATOR

Amiloride capsules 10mg once per day for 5 months

Drug: Amiloride

Placebo

PLACEBO COMPARATOR

Placebo capsules one per day for 5 months

Drug: Placebo

Interventions

Amiloride DRUG

Also known as: Midamor

Amiloride

Placebo DRUG

Placebo capsule identical in appearance to Amiloride 10mg capsule

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Participants with a first episode of unilateral optic neuritis
• 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 optic neuritis,
• A duration of disease of ≤10 years
• An EDSS (Expanded Disability Status Scale) of ≤3.
• No immune modulating treatment other than β-Interferon or glatiramer acetate at time of recruitment
• Able to be randomised within 28 days of onset of visual symptoms
• Visual acuity of ≤6/9
• Participant is willing and able to give informed consent for participation in the study and able to comply with study visits
• Male or Female, aged between18 - 55 years.
• Stable dose of current regular medication for at least 4 weeks prior to study entry.
• Participant has clinically acceptable urea and electrolytes and estimated glomerular filtration rate (eGFR) \>60
• Able and willing to comply with all study requirements.
• Willing to allow his or her General Practitioner to be notified of participation in the study.

You may not qualify if:

• Previous diagnosis of optic neuritis
• Any concomitant immune suppressing or immune modulating therapy excluding β-interferon or glatiramer acetate.
• Female participants who are pregnant, lactating or planning pregnancy during the course of the study.
• Concomitant potassium supplements, angiotensin converting enzyme inhibitors, angiotensin II antagonists, cyclosporine, tacrolimus or lithium
• Any contra-indication to MRI - severe claustrophobia, metal implant, pacemaker, etc.
• Participant who is terminally ill or is inappropriate for placebo medication
• Impaired renal function : eGFR ≤60, anuria, acute or chronic renal insufficiency and evidence of diabetic nephropathy
• Raised serum potassium (K+ \>5.5mmol/l)
• Diabetes
• Significant concomitant eye disease in either eye that may affect diseased or fellow eye results.
• 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 participant's ability to participate in the study.
• Participants who have participated in another research study involving an investigational product in the past 12 weeks.

Sponsors & Collaborators

• University of Oxford: lead
• Multiple Sclerosis Society of Great Britain and Northern Ireland: collaborator

Study Sites (1)

John Radcliffe Hospital

Oxford, OX3 9DU, United Kingdom

Location

Related Publications (2)

• McKee JB, Cottriall CL, Elston J, Epps S, Evangelou N, Gerry S, Kennard C, Kong Y, Koelewyn A, Kueker W, Leite MI, Palace J, Craner M. Amiloride does not protect retinal nerve fibre layer thickness in optic neuritis in a phase 2 randomised controlled trial. Mult Scler. 2019 Feb;25(2):246-255. doi: 10.1177/1352458517742979. Epub 2017 Nov 27.

  PMID: 29172994 DERIVED

• McKee JB, Elston J, Evangelou N, Gerry S, Fugger L, Kennard C, Kong Y, Palace J, Craner M. Amiloride Clinical Trial In Optic Neuritis (ACTION) protocol: a randomised, double blind, placebo controlled trial. BMJ Open. 2015 Nov 9;5(11):e009200. doi: 10.1136/bmjopen-2015-009200.

  PMID: 26553836 DERIVED

MeSH Terms

Conditions

Optic Neuritis; Multiple Sclerosis

Interventions

Amiloride

Condition Hierarchy (Ancestors)

Optic Nerve Diseases; Cranial Nerve Diseases; Nervous System Diseases; Eye Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Matthew Craner, MBChB PhD

  University of Oxford

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 27, 2013
• First Posted: March 1, 2013
• Study Start: February 1, 2013
• Primary Completion: November 1, 2015
• Study Completion: November 1, 2015
• Last Updated: May 17, 2018

Record last verified: 2018-05

Locations

GB (1)