Pregabalin in the Treatment of Essential Tremor
Condition: Essential Tremor
MeSH terms: Tremor; Essential Tremor
Study type: Interventional
Phase: Early Phase 1

Summary: 
      Pregabalin is approved for the treatment of nerve pain as well as an additional therapy in
      the treatment of seizures. In December 2004, Pfizer gained Food and Drug Administration (FDA)
      approval for use of pregabalin in nerve pain associated with diabetes and shingles; making it
      the first FDA-approved treatment for both of these nerve pain states.

      Tremor is uncontrolled trembling in part of the body. Essential tremor (ET) is associated
      with purposeful movement(e.g., holding a glass to drink, shaving, writing and buttoning a
      shirt). It occurs most often in the hands and head and also may affect the arms, voice box
      (larynx), trunk, and legs. ET is caused by abnormalities in areas of the brain that control
      movement. It usually does not result in serious complications.

      ET affects approximately 5 million people in the United States. Incidence is highest in
      people over the age of 60.

      ET usually develops gradually during middle age or later in life. Symptoms may remain mild or
      become more severe over time. Stress, fatigue, anxiety, and hot or cold weather can worsen
      the disorder. Severe tremor may cause difficulty doing activities of daily living, such as:

        -  Brushing hair and teeth

        -  Holding a glass without spilling

        -  Performing self-care (e.g., getting dressed, shaving, putting on makeup)

        -  Using eating utensils

        -  Writing and drawing

      The purpose of this pilot/feasibility study is to examine the tolerability and efficacy of
      Pregabalin in patients with ET.

      In other words, can patients diagnosed with ET tolerate high dose of pregabalin? Will the
      pregabalin be considered as an efficient medicine in the treatment of ET?
    

Detailed description: 
      Overview We propose a single site, double-blind, placebo-controlled, cross-over design. Drug
      will be administered in 75mg capsules with a target dose of 300 mg/day. Pregabalin will be
      titrated upward as described in the "Summary of Schedule" table with flexibility. During
      weeks 3-5 and 12-14, the investigator will have the option of increasing the study drug from
      2 capsules per day (150 mg vs. placebo) to 3 or 4 capsules per day if no benefit is noted. If
      the dose is increased, it must be done so at a rate of 150mg/day/week. Patients who can not
      tolerate a higher dose will be allowed to drop back to a previously tolerated dose but must
      be on that dose for one week prior to evaluation. After treatment and clinical assessment,
      study drug will be decreased by 150mg/day every 2 days until discontinuation. This pertains
      to both the wash out phase and at the end of the study. Both adverse events and need for drug
      titration will be conducted during the safety call.

      Identical assessments will be done at baseline and at the end of the treatment period for
      both drug and placebo. Half of the subjects (group A) will initiate with placebo and then
      crossover to drug. The other half (group B) will start treatment with pregabalin and then
      crossover to placebo.

      The primary endpoint will be the change in Fahn-Tolosa-Marin Tremor Rating Scale (TRS) from
      baseline. Scale has Parts A= (severity of rest, action & postural tremor in upper and lower
      extremities, face, voice, tongue, head & trunk), B= (severity of tremor writing, drawing &
      pouring), C= (functional disability while speaking, eating, drinking, maintaining hygiene,
      dressing & working) and the total summed.

      Other clinical assessments will include Clinical Global Impression of Change (CGI-C), Quality
      of Life in Essential Tremor Questionnaire (QUEST) maximum score =100, Hamilton Anxiety Scale
      (HAM-A) score 0-17 = mild, 18-24 = moderate, and 25-30 moderate to severe, and a sleep
      hygiene questionnaire rating across 5 domains- physical symptoms, energy & motivation,
      concentration, interpersonal relations, and psychological symptoms (HD-16). For the TRS,
      HAM-A, QUEST, and HD-16 higher scores represent increased symptom severity or diminished
      quality of life and the CGI-C is scored as follows: 1=very much improved, 2=much improved, 3=
      mildly improved, 4=no change, 5= mildly worse, 6= much worse, and 7=very much worse.
    

Intervention name(s): pregabalin (Lyrica); placebo
Intervention type(s): Drug; Drug
Intervention description(s): 75 mg bid to 300 mg bid based on per subject tolerability; up to 4 capsules bid as tolerated
Other intervention name(s): pregabalin
Intervention MeSH terms: Pregabalin
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Essential tremor; Activities of Daily Living (ADL's)