Trial Outcomes & Findings for Pregabalin in the Treatment of Essential Tremor (NCT NCT00646451)

Results Overview

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. .

Recruitment status

COMPLETED

Study phase

EARLY_PHASE1

Target enrollment

20 participants

Primary outcome timeframe

baseline to 6 weeks

Results posted on

2021-04-26

Participant Flow

Participant milestones

Participant milestones
Measure	Pregabalin First, Then Placebo Pregabalin: 75 mg bid to 300 mg bid based on per subject tolerability. Study crossover design. Patients were randomized for treatment with PGB or placebo, titrated over 6 weeks.	Placebo First, Then Pregabalin Placebo capsules: up to 4 capsules bid as tolerated. Study crossover design. Patients were randomized for treatment with PGB or placebo, titrated over 6 weeks.
Overall Study STARTED	10	10
Overall Study COMPLETED	6	10
Overall Study NOT COMPLETED	4	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Pregabalin First, Then Placebo Pregabalin: 75 mg bid to 300 mg bid based on per subject tolerability. Study crossover design. Patients were randomized for treatment with PGB or placebo, titrated over 6 weeks.	Placebo First, Then Pregabalin Placebo capsules: up to 4 capsules bid as tolerated. Study crossover design. Patients were randomized for treatment with PGB or placebo, titrated over 6 weeks.
Overall Study Adverse Event	3	0
Overall Study Exacerbation of pre-existing condition	1	0

Baseline Characteristics

Pregabalin in the Treatment of Essential Tremor

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Participants n=20 Participants Demographics and clinical characteristics of participants at study initiation are listed in Table 1 of the paper. Sixteen of 20 patients completed the study and were included in the analysis of drug efficacy (Table 2).
Age, Continuous	62.2 years STANDARD_DEVIATION 12.7 • n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants
Tremor Rating Scale (TRS) TRS Part A	18.3 units on a scale STANDARD_DEVIATION 6.0 • n=5 Participants
Tremor Rating Scale (TRS) TRS Part B	50.8 units on a scale STANDARD_DEVIATION 16.4 • n=5 Participants
Tremor Rating Scale (TRS) TRS Part C	43.1 units on a scale STANDARD_DEVIATION 16.3 • n=5 Participants
Tremor Rating Scale (TRS) TRS total	37.1 units on a scale STANDARD_DEVIATION 11.6 • n=5 Participants

PRIMARY outcome

Timeframe: baseline to 6 weeks

Population: Indistinguishable capsules and an identical titration protocol were used for PGB and placebo. Patients received the study drug at an initial dose of 75 mg twice daily, with upward titration to a target dose of 150 mg bid up to 300 mg bid. The study drug was increased at a rate of 150 mg/day/week.

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. .

Outcome measures

Outcome measures
Measure	1-Pregabalin n=20 Participants pregabalin : 75 mg bid to 300 mg bid based on per subject tolerability. Crossover study design and measure change in TRS Pregabalin group versus placebo group.	2-Placebo n=16 Participants placebo capsules : up to 4 capsules bid as tolerated. Crossover study design and measure change in TRS Pregabalin group versus placebo group.
Change in Tremor Rating Scale (TRS) Compared With Baseline. TRS Part A	2.4 units on a scale Standard Deviation 4.7	-0.2 units on a scale Standard Deviation 4.1
Change in Tremor Rating Scale (TRS) Compared With Baseline. Total TRS	5.1 units on a scale Standard Deviation 9.7	0.3 units on a scale Standard Deviation 4.6
Change in Tremor Rating Scale (TRS) Compared With Baseline. TRS Part B	6.7 units on a scale Standard Deviation 12.3	3.6 units on a scale Standard Deviation 6.6
Change in Tremor Rating Scale (TRS) Compared With Baseline. TRS Part C	4.5 units on a scale Standard Deviation 13.9	-1.5 units on a scale Standard Deviation 12.8

SECONDARY outcome

Timeframe: baseline to 6 weeks

Population: Change in secondary measures of efficacy compared with baseline.

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 \[7\], \[8\] and \[9\]. 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.

Outcome measures

Outcome measures
Measure	1-Pregabalin n=20 Participants pregabalin : 75 mg bid to 300 mg bid based on per subject tolerability. Crossover study design and measure change in TRS Pregabalin group versus placebo group.	2-Placebo n=16 Participants placebo capsules : up to 4 capsules bid as tolerated. Crossover study design and measure change in TRS Pregabalin group versus placebo group.
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) HAM-A	1.1 units on a scale Standard Deviation 5.2	4.1 units on a scale Standard Deviation 5.4
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) CGI-C	3.9 units on a scale Standard Deviation 1.3	3.8 units on a scale Standard Deviation 0.5
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) QUEST	8.0 units on a scale Standard Deviation 20.3	-9.7 units on a scale Standard Deviation 14.5
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) HD-16	32.2 units on a scale Standard Deviation 146.8	-38.6 units on a scale Standard Deviation 99.3

Adverse Events

Pregabalin

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Pregabalin n=20 participants at risk pregabalin: 75 mg bid to 300 mg bid based on per subject tolerability	Placebo n=18 participants at risk placebo capsules: up to 4 capsules bid as tolerated
General disorders drowsiness	25.0% 5/20 • Number of events 5 • 14 weeks of study duration	16.7% 3/18 • Number of events 3 • 14 weeks of study duration
General disorders dizziness	20.0% 4/20 • Number of events 4 • 14 weeks of study duration	5.6% 1/18 • Number of events 1 • 14 weeks of study duration
General disorders fatigue	15.0% 3/20 • Number of events 3 • 14 weeks of study duration	0.00% 0/18 • 14 weeks of study duration
General disorders instability	15.0% 3/20 • Number of events 3 • 14 weeks of study duration	5.6% 1/18 • Number of events 1 • 14 weeks of study duration
General disorders insomnia	0.00% 0/20 • 14 weeks of study duration	11.1% 2/18 • Number of events 2 • 14 weeks of study duration
General disorders headache	0.00% 0/20 • 14 weeks of study duration	11.1% 2/18 • Number of events 2 • 14 weeks of study duration

Additional Information

Dr. Joseph Jankovic

Baylor College of Medicine

Phone: 713-798-6556

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place