Amiloride Hydrochlorothiazide as Treatment of Acute Inflammation of the Optic Nerve
Recruitment status was: Recruiting
|Optic; Neuritis, With Demyelination||Drug: Amiloride hydrochlorothiazide Drug: Sugar pill||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||A Randomized, Placebo-Controlled, Double-Blind, Phase IIa Study of Amiloride in the Treatment of Acute Autoimmune Optic Neuritis|
- Change in thickness of retinal nerve fiber layer (RNFL) [ Time Frame: Baseline versus follow-up at 24 weeks ]
|Study Start Date:||March 2014|
|Estimated Study Completion Date:||April 2016|
|Estimated Primary Completion Date:||April 2016 (Final data collection date for primary outcome measure)|
Active Comparator: Amiloride hydrochlorothiazide
5,68 mg Amiloridhydrochloride 2H20 (analogue 4,32 mg Amilorid) und 50 mg Hydrochlorothiazid. Trade name of the agent: Amilostad HCT 5/50mg tablets Manufacturer: Stada initial dose: 1 x 5/50mg once daily target dose: 2 x 5/50mg once daily Patients will be provided with capsules (size 00) containing one tablet of study medication 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
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.
Placebo Comparator: Sugar pill
Patients will be provided with capsules (size 00) containing sugar and instructed to take these capsules once daily in the morning together with breakfast.
Drug: Sugar pill
Other Name: placebo
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01879527
|Contact: Fritz Leutmezer, MD||+43140400 ext firstname.lastname@example.org|
|Medical University of Vienna, Department of Neurology||Recruiting|
|Vienna, Austria, 1090|
|Contact: Fritz Leutmezer, MD +43140400 ext 3120 email@example.com|
|Principal Investigator: Fritz Leutmezer|
|Principal Investigator:||Fritz Leutmezer, MD||Medical University of Vienna|