A 17 Week, Investigator-initiated, Single-center, Double-blind, Randomized, Placebo-controlled, Cross-over Trial of Pregabalin in Essential Tremor
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Change in Tremor Rating Scale (TRS) Compared With Baseline.
研究概览
简要总结
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?
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects must be between the ages of 18 and 80 inclusive.
- •Each subject must have current manifestations of ET symptoms based on the Tremor Investigational Group (TRIG) criteria for definite or probable ET: - Moderate or severe tremor in head or arms for at least 3 years duration. - No present causes of enhanced physiologic tremor. - No recent exposure to tremorogenic drugs or drug withdrawal states. - No direct or indirect trauma to the nervous system within 3 months preceding the onset of tremor. - No historic or clinical evidence of psychogenic tremor origin.
- •Subjects with a history of seizures are eligible.
- •Subjects must be in generally good health as evidenced by previous medical history and clinical examination.
- •Patients will be allowed to take Beta-blockers but will not be allowed to take any other medication for tremor (primidone, topiramate, benzodiazepines, etc.) An evening dose of a benzodiazepine to improve sleep is acceptable. They must have been on a stable dose of any existing beta-blocker for 4 weeks prior to entry into the study and will not be allowed to change the dose of that medication throughout the controlled portion of the study. Any medication discontinued during screening in order to comply with these criteria must be stopped for 5 half-lives prior to study initiation.
- •Subjects must be accessible by telephone.
- •If the subject is a female of childbearing age, she must have had a hysterectomy, tubal ligation, otherwise be incapable of pregnancy, or have practiced one of the following methods of contraception for at least one month prior to study entry (or a negative urine pregnancy test within one week of study entry): - Hormonal contraceptives - Spermicide and barrier - Intrauterine device - Partner sterility
- •Prior to participation in this study, each subject must sign an informed consent.
排除标准
- •Patients do not meet TRIG criteria for probable ET.
- •Subjects who are not able to abstain from alcohol for 24 hours prior to each evaluation.
- •Patients who can not maintain an identical dose of any medicine that may affect tremor during their entire study involvement.
- •Subjects who have exhibited any psychotic symptomatology.
- •Subjects who have known renal deficiencies.
- •Subjects who have been intolerant of pregabalin in the past
- •Prior surgical treatment for tremor.
- •Patients currently taking more than a single drug for ET.
- •Patients taking anti-seizure medications.
- •Breast feeding or pregnant females.
研究组 & 干预措施
Pregabalin (Lyrica)
Pregabalin (Lyrica) 75 mg bid to a maximum dose of 300 mg bid
干预措施: pregabalin (Lyrica) (Drug)
Placebo
Placebo to 4 capsules bid
干预措施: placebo (Drug)
结局指标
主要结局
Change in Tremor Rating Scale (TRS) Compared With Baseline.
时间窗: 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. .
次要结局
- 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)(baseline to 6 weeks)
研究者
Joseph Jankovic
Principal Investigator
Baylor College of Medicine