Acamprosate and Methazolamide for Essential Tremor

Phase 2

Withdrawn

• Conditions: Essential Tremor
• Interventions: Drug: Acamprosate; Drug: Placebo; Drug: Methazolamide

• Registration Number: NCT06312800
• Lead Sponsor: Henry Ford Health System

Brief Summary

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).

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 (FMTRS) 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 near by 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 tablet 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 assessement 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 Timeline

• Study First Submitted: 2015-07-13
• Study Start: 2016-03
• Primary Completion: 2017-06
• Study Completion: 2017-12
• Status Verified: 2024-03
• Study First Submitted QC: 2024-03-08
• Last Update Submitted: 2024-03-08
• Study First Posted: 2024-03-15
• Last Update Posted: 2024-03-15

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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 [1] 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 & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Acamprosate	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.
Placebo	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
Methazolamide	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

Primary Outcome Measures

Name	Time	Method
Fahn-Talosa-Marin rating scale (FTMRS) Part A	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).

Trial Locations

Locations (1)

Henry Ford West Bloomfield Hospital; 🇺🇸 West Bloomfield, Michigan, United States