Amiloride Hydrochlorothiazide as Treatment of Acute Inflammation of the Optic Nerve

Optic; Neuritis, With Demyelination Clinical Trial

Official title:

A Randomized, Placebo-Controlled, Double-Blind, Phase IIa Study of Amiloride in the Treatment of Acute Autoimmune Optic Neuritis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01879527
• Other study ID #: SSP-2
• Secondary ID: 2012-005113-39
• Status: Recruiting
• Phase: Phase 2
• First received: June 13, 2013
• Last updated: May 8, 2015
• Start date: March 2014
• Est. completion date: April 2016

Study information

• Verified date: May 2015
• Source: Medical University of Vienna
• Contact: Fritz Leutmezer, MD
• Phone: +43140400
• Email: fritz.leutmezer[@]meduniwien.ac.at
• Is FDA regulated: No
• Health authority: Austria: Austrian Federal Office for Safety in Health Care
• Study type: Interventional

Clinical Trial Summary

Following acute inflammation of the optic nerve region, as commonly seen in multiple sclerosis patients, the optic nerve often undergoes atrophy, thus representing permanent damage. Data from animal studies suggest that amiloride may prevent this process. The aim of this study is to assess a potential neuroprotective effect of amiloride in acute autoimmune inflammation of the optic nerve region.

Description:

Recent studies have shown that the acid-sensing ion channel 1 (ASIC1) contributes to the axonal degeneration in CNS lesions Physiologically, ASIC1 has been described as a postsynaptic proton receptor on hippocampal neurons influencing the intracellular Ca2+ concentration. In MS, ASIC1 seems to activate under acidic conditions predominating in the inflammatory CNS lesions leading to a Na+ and Ca2+ overload and consecutive damage and apoptosis of axons. Consecutively, in a MS mousemodel axonal damage was significantly less pronounced after administering amiloride, a clinically safe blocker of ASICs. So ASIC1 seems to play a major role in axonal degeneration in MS. To our knowledge no clinical studies have tested those promising in vitro results in humans so far.

Only one retrospective registry-based cohort study was performed. This study showed no difference in the risk of incident MS or hospitalization and death among MS patients using amilorid compared to those using thiazide diuretics. However, this study has numerous limitations with respect to it's retrospective designone and the fact that amilorid users were at the vast majority older individuals. Such a late stage of the MS course does not seem to be the best window of opportunity for interventions with neuroprotective agents. Moreover, death may be a too multifactorial parameter to correspond with axonal damage alone. Consequently, a more sensitive parameter for axonal damage in MS is needed to test the impact of amiloride on neuroprotection and repair.Based on the findings described above we intend to assess the potential neuroprotective effect of amiloride hydrochlorothiazide (Amilostad HCT®) in patients with optic neuritis (ON), which has already been demonstrated in a mouse model. ON is one of the most common manifestations of MS and has already been proven appropiate to test neuroprotective agents.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 78
• Est. completion date: April 2016
• Est. primary completion date: April 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

Patients between 18 and 50 years of age with a first episode of optic neuritis (ON) and a visual acuity decreased to <0,6 will be eligible for inclusion in the study. Diagnosis of ON has to be confirmed by an ophthalmologist. Onset of symptoms has to be within 10 days prior to inclusion into the study

Exclusion Criteria:

• Known allergy or hypersensitivity to amilostad HCT or any of its ingredients

• Known allergy or hypersensitivity to other sulphonamide-derived drugs

• Impaired renal function or any known renal disease

• Intake of other potassium-conserving diuretics

• Intake of potassium supplements or a special potassium rich diet

• Intake of spironolactone or triamterene

• Moderate to severe hepatic failure

• Morbus Addison

• Known hypercalcaemia

• Intake of lithium therapy

• Blood urea > 10mmol/l

• Diabetes mellitus

• History of ON or any other ocular disease (affected as well as unaffected eye)

• Pregnancy or lactation period

• Treatment with corticosteroids or amiloride within 30 days prior to the inclusion into the study

• Use of any immunomodulatory or immunosuppressive agents anytime in the past

• Dearrangement of serum sodium or potassium levels on the lab

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Neuritis
• Optic Neuritis
• Optic; Neuritis, With Demyelination

Intervention

Drug:
• Amiloride hydrochlorothiazide
Blinding will be done by over-encapsulating amiloride HCT tablets and providing corresponding placebo capsules.Patients will be provided with capsules (size 00) containing one tablet of study medication (Amilostad HCT 5/50mg tablet or placebo) and instructed to take these capsules once daily in the morning together with breakfast. Visit 2 will be scheduled one week after baseline and at visit 2 patients will be provided with capsules containing two tablets of study medication. This maintenance dose will not be changed throughout the remaining study period. Placebo will be administered in the exact same manner.
• Sugar pill
containing placebo

Locations

Country	Name	City	State
Austria	Medical University of Vienna, Department of Neurology	Vienna

Sponsors (1)

Lead Sponsor	Collaborator
Medical University of Vienna

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in thickness of retinal nerve fiber layer (RNFL)		Baseline versus follow-up at 24 weeks	No