Clinical trial NCT06312800: Acamprosate and Methazolamide for Essential Tremor
Official title: Acamprosate and Methazolamide for Essential Tremor: a Randomized Clinical Trial
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Essential Tremor
Keywords: Essential Tremor
Lead sponsor: Henry Ford Health System
Sponsor class: OTHER
First posted: 2024-03-15
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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 (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.

Eligibility criteria: 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

Primary outcomes:
measure: Fahn-Talosa-Marin rating scale (FTMRS) Part A
timeFrame: 11 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: West Bloomfield
country: United States
facility: Henry Ford West Bloomfield Hospital
state: Michigan
Study officials:
affiliation: Henry Ford Health System
name: Peter LeWitt, M.D.
role: PRINCIPAL_INVESTIGATOR
References: