Ethanol Response in Essential Tremor: Clinical and Neurophysiological Correlates

NCT01200966 | Completed

• 2 other identifiers: 10019910-N-0199
• Study Type: observational
• Target: 96
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- Essential tremor (ET) is a neurological disorder involving uncontrollable shaking, which over time can interfere with mobility and affect routine aspects of daily living. Several medications are used to treat ET, but these medications are often only partially effective and can have side effects. About two-thirds (66%) of people with ET have some relief from drinking alcohol, which suggests that alcohol affects the part of the brain causing the tremor. However, more research is needed to better understand the effects of alcohol or what areas of the brain might be important in the response. Objectives:

• To study to what extent alcohol is reducing tremor in a group of patients with essential tremor.
• To use transcranial magnetic stimulation to study the effects of alcohol on essential tremor. Eligibility: \- Individuals who are at least 21 years of age, have been diagnosed with essential tremor and have tremor in both hands, and can tolerate being off all medications for essential tremor for up to 4 weeks. Design:
• This study has one screening visit (1 to 2 hours), followed by one study visit (3 to 5 hours). Participants might be asked to also take part in one additional study visit (3 to 5 hours). The maximum period between the study visits is 3 months.
• Participants will be screened with a medical history, physical examination, and blood tests. At this visit, participants will receive information about how to safely taper off their current ET medications before the start of the study.
• Participants must be willing to abstain from drinking any alcohol or caffeine (or consuming foods with caffeine such as chocolate) for at least 2 days before the study visits. Participants must also fast overnight (for at least 8 hours) before the study visits.
• At the first study visit, participants will receive a single drink of alcohol (mixed with a noncaffeinated drink) and will complete movement tests to determine whether the alcohol improves the tremor. Alcohol levels will be monitored throughout the visit.
• At the second study visit, participants will have an electrocardiogram to measure heart electrical activity and determine if they are able to safely have transcranial magnetic stimulation. Participants will then receive an intravenous infusion of alcohol and complete questionnaires during the infusion to provide information about its effects. Then, transcranial magnetic stimulation will be used to study brain electrical activity, as well as muscle movements and tremor activity, while under the influence of the alcohol infusion.
• After each study visit, participants will remain at the clinical center until the effects of the alcohol have worn off. Participants will be able to resume taking their ET medications after the end of the study.

Conditions

Essential Tremor

Keywords

Essential Tremor; Transcranial Magnetic Stimulation (TMS); Ethanol; Alcohol; Alcohol Clamp; ET

Outcome Measures

Primary Outcomes (2)

• Phase 1: To objectively determine the rate of ethanol responders vs. non-responders in a prospective sample of ET patients.

• Phase 2: To evaluate changes of SICI in responding vs. non-responding ET patients during a continuous ethanol administration

Secondary Outcomes (2)

• Phase 1: To correlate spirographic and clinical response in both hands with breath-alcohol-levels, acquired using a Breathalyzer at constant intervals after ethanol administration.

• Phase 2: To evaluate changes additional TMS measures between groups

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of essential tremor with bilateral hand tremor as the predominant feature
• Unequivocal spirographic tremor of both hands on screening examination
• Subjects must be willing and safely able to comply with the study protocol and therefore abstain from any medication for the treatment of tremor for a period of at least 5 plasma half-lives of the individual drug prior to study participation. (For Propranolol/Inderal , Gabapentin/Neurontin this will be 1 day; for Primidone/Mysoline : 26 days).
• Subjects must be willing to refrain from alcohol and drinks or food containing caffeine starting 48 hours prior to the study visit(s)

You may not qualify if:

• Patients with any other significant pathological finding in the neurological examination other than typical symptoms of ET
• Acute or chronic severe medical conditions which would preclude the subject from participating (e.g., severe heart disease NYHA grade 3 or 4, renal failure, hepatic failure, lung disease, uncontrolled hyperthyroidism)
• Subjects with active or past alcohol abuse or dependence
• Elevated liver function parameters (AST, ALT, GGT), higher than the 1.5 fold upper limit of the normal range (as defined by the NIH Clinical Center Laboratory Medicine Department). The limit for AST therefore will be 51 U/l, for ALT 62 U/L, and GGT 128 U/l.
• Female subjects who are pregnant or lactating
• Subjects aged \< 21 years
• Subjects with unable or unwilling to give informed consent
• Subjects unable or unwilling to cooperate with study requirements Use of prescription or OTC medications that interact with ethanol or influence brain excitability (e.g. hypnotic, antiepileptic, antipsychotic medication, stimulants, antihistamines, muscle relaxants, etc.).
• Known flushing symptoms after alcohol intake or allergy to alcohol.
• History of seizure disorder or hearing loss
• Presence of pacemaker, implanted medical pump, metal plate or metal object in skull or eye.

Sponsors & Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Louis ED, Ottman R, Hauser WA. How common is the most common adult movement disorder? estimates of the prevalence of essential tremor throughout the world. Mov Disord. 1998 Jan;13(1):5-10. doi: 10.1002/mds.870130105.

  PMID: 9452318 BACKGROUND

• Deuschl G, Bain P, Brin M. Consensus statement of the Movement Disorder Society on Tremor. Ad Hoc Scientific Committee. Mov Disord. 1998;13 Suppl 3:2-23. doi: 10.1002/mds.870131303.

  PMID: 9827589 BACKGROUND

• Wells JN, Shirodkar AV, Knevel AM. Aziridine derivatives as potential monoamine oxidase inhibitors. J Med Chem. 1966 Mar;9(2):195-7. doi: 10.1021/jm00320a009. No abstract available.

  PMID: 5911798 BACKGROUND

MeSH Terms

Conditions

Essential Tremor

Condition Hierarchy (Ancestors)

Movement Disorders; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Mark Hallett, M.D.

  National Institute of Neurological Disorders and Stroke (NINDS)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2010
• First Posted: September 14, 2010
• Study Start: August 30, 2010
• Study Completion: January 4, 2017
• Last Updated: December 17, 2019

Record last verified: 2017-01-04

Locations

US (1)