Pregabalin in the Treatment of Essential Tremor
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|ClinicalTrials.gov Identifier: NCT00646451|
Recruitment Status : Completed
First Posted : March 28, 2008
Results First Posted : March 12, 2021
Last Update Posted : April 26, 2021
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?
|Condition or disease||Intervention/treatment||Phase|
|Essential Tremor||Drug: pregabalin (Lyrica) Drug: placebo||Early Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||20 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||A 17 Week, Investigator-initiated, Single-center, Double-blind, Randomized, Placebo-controlled, Cross-over Trial of Pregabalin in Essential Tremor|
|Study Start Date :||June 2006|
|Actual Primary Completion Date :||December 2008|
|Actual Study Completion Date :||December 2008|
Active Comparator: Pregabalin (Lyrica)
Pregabalin (Lyrica) 75 mg bid to a maximum dose of 300 mg bid
Drug: pregabalin (Lyrica)
75 mg bid to 300 mg bid based on per subject tolerability
Other Name: pregabalin
Placebo Comparator: Placebo
Placebo to 4 capsules bid
up to 4 capsules bid as tolerated
- Change in Tremor Rating Scale (TRS) Compared With Baseline. [ Time Frame: baseline to 6 weeks ]
Change from baseline in the overall TRS score obtained at the final evaluation (end of study). The overall TRS score will be derived from the three TRS subscales. The minimum and maximum score for part A is 0-80, part B is 0-36, and part C is 0-28 giving a maximum score of 144. TRS part A rates the severity of resting, postural and action tremor in upper and lower extremities, face, tongue, voice, head and trunk. Part B rates the severity of upper extremity tremor while writing, drawing, and pouring liquid. Part C rates functional disability of tremor while speaking, eating, drinking, maintaining hygiene, dressing, and working. Higher scores represent increased symptom severity or diminished quality of life.
- Secondary Outcome Measures Quality of Life in Essential Tremor (QUEST), Hamilton Anxiety Scale (HAM-A), Hotel Dieu-16 a Sleep Hygiene Questionnaire(HD-16), and Clinical Clobal Impression-Change Scale (CGI-C) [ Time Frame: baseline to 6 weeks ]The Quality of Life in Essential Tremor Questionnaire (QUEST), Hamilton Anxiety scale (HAM-A) and Hotel Dieu-16 (HD-16) were scored as per published guidelines ,  and . The QUEST rates patient perception as influenced by tremor across 5 domains. A QUEST score will be between 0 and 120 with 0 = no essential tremor and 120 = severe essential tremor. The HAM-A rates the severity of anxiety symptomatology across 14 parameters. Scores of 14-17 = mild anxiety, 18-24 = moderate anxiety, and 25-30 = severe anxiety; The HD-16 rates insomnia-related quality of life across five domains. An HD-16 score of 73.1 - 248.5 = severe insomnia, 61-73.1 = mild insomnia, and 0 - 61 = good sleeper. For the scales, HAM-A, QUEST and HD-16, higher scores represent increased symptom severity or diminished quality of life. CGI-C was 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00646451
|United States, Texas|
|PDCMDC 6550 Fannin, Suite 1801|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Joseph Jankovic, MD||Baylor College of Medicine|