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Amiloride Hydrochlorothiazide as Treatment of Acute Inflammation of the Optic Nerve

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2015 by Medical University of Vienna
Sponsor:
Information provided by (Responsible Party):
Prof. Fritz Leutmezer, Medical University of Vienna
ClinicalTrials.gov Identifier:
NCT01879527
First received: June 13, 2013
Last updated: May 8, 2015
Last verified: May 2015
  Purpose
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.

Condition Intervention Phase
Optic; Neuritis, With Demyelination
Drug: Amiloride hydrochlorothiazide
Drug: Sugar pill
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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

Resource links provided by NLM:


Further study details as provided by Medical University of Vienna:

Primary Outcome Measures:
  • Change in thickness of retinal nerve fiber layer (RNFL) [ Time Frame: Baseline versus follow-up at 24 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 78
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)
Arms Assigned Interventions
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.
Other Names:
  • Marketing Authorisation number: 1-22734
  • Trade name: Amilostad HCT
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
containing placebo
Other Name: placebo

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01879527

Contacts
Contact: Fritz Leutmezer, MD +43140400 ext 3120 fritz.leutmezer@meduniwien.ac.at

Locations
Austria
Medical University of Vienna, Department of Neurology Recruiting
Vienna, Austria, 1090
Contact: Fritz Leutmezer, MD    +43140400 ext 3120    fritz.leutmezer@meduniwien.ac.at   
Principal Investigator: Fritz Leutmezer         
Sponsors and Collaborators
Medical University of Vienna
Investigators
Principal Investigator: Fritz Leutmezer, MD Medical University of Vienna
  More Information

Responsible Party: Prof. Fritz Leutmezer, MD, Medical University of Vienna
ClinicalTrials.gov Identifier: NCT01879527     History of Changes
Other Study ID Numbers: SSP-2  2012-005113-39 
Study First Received: June 13, 2013
Last Updated: May 8, 2015
Health Authority: Austria: Austrian Federal Office for Safety in Health Care

Additional relevant MeSH terms:
Optic Neuritis
Demyelinating Diseases
Neuritis
Nervous System Diseases
Peripheral Nervous System Diseases
Neuromuscular Diseases
Optic Nerve Diseases
Cranial Nerve Diseases
Eye Diseases
Hydrochlorothiazide
Amiloride
Amiloride, hydrochlorothiazide drug combination
Antihypertensive Agents
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Sodium Chloride Symporter Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Acid Sensing Ion Channel Blockers
Sodium Channel Blockers
Epithelial Sodium Channel Blockers
Diuretics, Potassium Sparing

ClinicalTrials.gov processed this record on September 29, 2016