Acamprosate and Methazolamide for Essential Tremor

September 23, 2024 updated by: Peter LeWitt MD, Henry Ford Health System

Acamprosate and Methazolamide for Essential Tremor: a Randomized Clinical Trial

This is an investigator initiated study is designed to evaluate the anti-tremor benefits of two marketed medications, methazolamide and acamprosate in subjects with a diagnosis of essential tremor (ET).

Study Overview

Status

Status

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Withdrawn

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

This is an investigator-initiated study is designed to evaluate the anti-tremor benefits of two marketed medications, methazolamide and acamprosate in subjects with a diagnosis of essential tremor (ET). Methazolamide is approved by the FDA to treat glaucoma. Acamprosate is approved by the FDA and used in the treatment of alcoholism. Some subjects using these medications for those indications incidentally reported that they had improvement in their essential tremor symptoms.

The primary objective of this study is the change in the upper extremity tremor scores assessed by one of the tremor rating scales (FTMRS) compared to baseline. This scale has been used in previous reported studies. Secondary objectives will be to evaluate the change in the ratings on several scales between placebo and study medication treatment. Additionally, tremor amplitude will be measured with device called Kinesia HomeView. This has a sensor unit that is slipped over a finger and transmits information to a nearby computer. This device has been used by our staff in other clinical studies at our site to evaluate tremor symptoms.

The study is a double blind, parallel design with three separate treatment arms, each 3 weeks long . One arm is placebo, the other two are conventional dosing of either acamprosate (333 mg tablets TID) or methazolamide (50 mg tablets TID). Subjects who have ET and meet criteria will be randomized in varied order to undergo all three treatments. There will be a one-week washout period between arms of study treatments where subject are not on any study medication. Subjects who qualify will be titrated on every three days up to a final dose of one table,t three times a day at mealtimes by day 7. They will then be evaluated after two weeks and three weeks on this dose.

There are 7 visits for the study. Consent will be reviewed and signed at the beginning of visit one. All study visits include vital sign assessment, neurological exam, suicidality, tremor rating scales and Kinesia recoding. Quality of life questionnaire will be completed weekly after start. Visit one will also include collecting information on medical history, medication history and current medication. A physical exam will be done on visit one and at the end of the study. For qualifying patients, study medication will be dispensed at the end of visit one and instructions provided for titrating. Medication will be collected and counted at each visit, each arm will last for 3 weeks, with subject ET symptom assessment at week 2 and 3. After completion of week 3 assessments, all study medication will be returned, and they will change dosing to the next assigned arm where the same assessment cycle is undergone. Study medication and directions will be provided with directives to start dosing after one week wash out. After trial arm 3, subject trial participation is completed. Adverse events are assessed weekly from starting trial medication at visit one until one week after end of trial.

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

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 Locations

  • United States
    • Michigan
      • West Bloomfield, Michigan, United States, 48322
        • Henry Ford West Bloomfield Hospital

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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  1. bilateral, largely symmetric postural or kinetic tremor involving hands and forearms that is visible and persistent. Subjects need to meet a FTMRS. Part A motor score of at least 2 ("Moderate amplitude, 0.5-1 cm, may be intermittent") in the dominant upper limb for action or postural tremor (or both).
  2. additional tremor (head, voice, or lower extremity) may also be present but in the absence of abnormal posturing so as to suggest the diagnosis of dystonia.

Exclusion Criteria:

  1. other abnormal neurologic signs
  2. the presence of known causes of enhanced physiologic tremor, including current or recent exposure to drugs known to cause or exacerbate tremor, or the presence of a drug -withdrawal state
  3. historical or clinical evidence of psychogenic tremor
  4. convincing evidence of sudden onset or other evidence of stepwise deterioration
  5. primary orthostatic tremor
  6. isolated position-specific or task-specific tremors, including occupational tremors and primary writing tremor
  7. tremor possibly or probably due to other neurological disorders (such as Parkinson's disease, cerebellar degeneration, and hyperthyroidism)
  8. prior brain surgery (including deep brain stimulation of Gamma Knife treatment) for thalamotomy
  9. known allergy to the study medications
  10. clinically significant liver, kidney, or cardiac abnormalities

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: Crossover 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.
Experimental: Acamprosate
Commercially available Acamprosate 333 mg tablets will be administered three times daily. Subjects will be started with one tablet with breakfast for 3 days, then one tablet with breakfast and dinner for 3 days, then one tablet 3 times a day for the next 15 days. Intervention order of medication trials will be determined by biostatistician.
Drug: Acamprosate
Randomized allocation of treatments will guide the dispensation of treatments in one of 6 possible sequences--ex, M (methazolamide)- P(placebo)-A (Acamprosate); or PAM or MAP or PMA or AMP or APM. Biostatistician will devise medication randomization strategies and investigators and staff will be blinded.
Active Comparator: Placebo
Placebo tablets are not available from the manufacturer for either of these drugs which are marketed as white tablets about the size of an aspirin tablet. Custom made placebo tablets will be purchased that are about that size. While not ideal , the extent of disguising the drug identity should be adequate with this. The placebo tablets will be administered three times daily. Subjects will be started with one tablet with breakfast for 3 days, then one tablet with breakfast and dinner for 3 days, then one tablet 3 times a day for the next 15 days. Intervention order of medication trials will be determined by biostatistician
Drug: Placebo
Randomized allocation of treatments will guide the dispensation of treatments in one of 6 possible sequences--ex, M (methazolamide)- P(placebo)-A (Acamprosate); or PAM or MAP or PMA or AMP or APM. Biostatistician will devise medication randomization strategies and investigators and staff will be blinded.
Experimental: Methazolamide
Commercially available methazolamide 50 mg tablets will be administered three times daily. Subjects will be started with one tablet with breakfast for 3 days, then one tablet with breakfast and dinner for 3 days, then one tablet 3 times a day for the next 15 days. Intervention order of medication trials will be determined by biostatistician
Drug: Methazolamide
Randomized allocation of treatments will guide the dispensation of treatments in one of 6 possible sequences--ex, M (methazolamide)- P(placebo)-A (Acamprosate); or PAM or MAP or PMA or AMP or APM. Biostatistician will devise medication randomization strategies and investigators and staff will be blinded.

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
Measure Description
Time Frame
Fahn-Talosa-Marin rating scale (FTMRS) Part A
Time Frame: 11 weeks

Comparison of placebo to each of the two medications for the sum of upper extremity postural and action tremor scores from the Fahn-Talosa-Marin rating scale (FTMRS).

The Fahn-Tolosa-Marin Clinical Rating Scale for Tremor (FTM) has been used for essential tremor (ET), but its anchors for ratings from 0 to 4 of upper limb tremor are probably too low for patients with severe tremor (tremor amplitude >4 cm; grade 4).
11 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.
Henry Ford Health System

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: Peter LeWitt, M.D., Henry Ford Health System

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 (Estimated)

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, 2016

Primary Completion (Actual)

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.
June 1, 2017

Study Completion (Actual)

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.
December 1, 2017

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).
July 13, 2015

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.
March 8, 2024

First Posted (Actual)

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.
March 15, 2024

Study Record Updates

Last Update Posted (Actual)

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.
September 25, 2024

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.
September 23, 2024

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.
September 1, 2024

More Information

Terms related to this study

Keywords

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.
  • LeWitt02

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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