Amiloride Hydrochlorothiazide as Treatment of Acute Inflammation of the Optic Nerve

May 8, 2015 updated by: Prof. Fritz Leutmezer, Medical University of Vienna

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
78

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Austria
      • Vienna, Austria, 1090
        • Recruiting
        • Medical University of Vienna, Department of Neurology
        • Contact:
        • Principal Investigator:
          • Fritz Leutmezer

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 50 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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 Names:
  • placebo

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Change in thickness of retinal nerve fiber layer (RNFL)
Time Frame: Baseline versus follow-up at 24 weeks
Baseline versus follow-up at 24 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Medical University of Vienna

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Fritz Leutmezer, MD, Medical University of Vienna

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 2014

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 1, 2016

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 1, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 13, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 13, 2013

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 18, 2013

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 12, 2015

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 8, 2015

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2015

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • SSP-2
  • 2012-005113-39 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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