Essential TremorEarly Phase 1NCT00646451
Pregabalin in the Treatment of Essential Tremor
A Early Phase 1 study testing pregabalin (Lyrica) in people with Essential Tremor, run by Baylor College of Medicine at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Essential Tremor
- What is being tested?
- pregabalin (Lyrica)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2006to Dec 2008
- Phase
- Early Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 10Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
PDCMDC 6550 Fannin, Suite 1801
Houston, Texas, 77030
About this study
Official title: A 17 Week, Investigator-initiated, Single-center, Double-blind, Randomized, Placebo-controlled, Cross-over Trial of Pregabalin in Essential Tremor
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.
Read more
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?
Read the 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.
- Conditions
- Essential Tremor
- Being tested
- pregabalin (Lyrica), placebo
- Keywords
- Essential tremor, Activities of Daily Living (ADL's)
- Medical subject headings
- Essential Tremor
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
pregabalin (Lyrica)Drug
Also called pregabalin
75 mg bid to 300 mg bid based on per subject tolerability
placeboDrug
up to 4 capsules bid as tolerated
| Study group | Role | What they receive |
|---|---|---|
| Pregabalin (Lyrica) | Active comparator | Pregabalin (Lyrica) 75 mg bid to a maximum dose of 300 mg bid Receives: Drug: pregabalin (Lyrica) |
| Placebo | Placebo comparator | Placebo to 4 capsules bid Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Tremor Rating Scale (TRS) Compared With Baseline.
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.
.
Measured: baseline to 6 weeks
Secondary outcomes (1)
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)
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.
Measured: baseline to 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Mar 2008 (estimated)
- Study startJun 2006
- Primary completionDec 2008
- Study completionDec 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Essential TremorStudies of the same condition, open and under way.
- More trials run by Baylor College of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baylor College of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer
- Responsible party
- Principal investigator, Joseph Jankovic, Baylor College of Medicine
- Investigators
- Joseph Jankovic, MD, Principal investigator, Baylor College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00646451
- Sponsor's protocol ID
- H-19086
- Status last verified
- Apr 2021
- First submitted
- 28 Dec 2007
- Last updated
- 26 Apr 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Ferrara JM, Kenney C, Davidson AL, Shinawi L, Kissel AM, Jankovic J. Efficacy and tolerability of pregabalin in essential tremor: a randomized, double-blind, placebo-controlled, crossover trial. J Neurol Sci. 2009 Oct 15;285(1-2):195-7. doi: 10.1016/j.jns.2009.06.044. Epub 2009 Jul 25.
PubMed 19631949
Study at a glance
From the registry record, last updated by the sponsor on 26 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A 17 Week, Investigator-initiated, Single-center, Double-blind, Randomized, Placebo-controlled, Cross-over Trial of Pregabalin in Essential Tremor
- ClinicalTrials.gov ID
- NCT00646451
- Acronym / sponsor ID
- H-19086
- Conditions
- Essential Tremor
- Keywords
- Essential tremor, Activities of Daily Living (ADL's)
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Baylor College of MedicineUniversity, hospital or other
- Collaborators
- Pfizer
- Study start
- Jun 2006
- Primary completion
- Dec 2008 (actual)
- Study completion
- Dec 2008 (actual)
- First posted
- 28 Mar 2008 (estimated)
- Results
- Posted 12 Mar 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pregabalin (Lyrica) | Active comparator | Drug: pregabalin (Lyrica)Pregabalin (Lyrica) 75 mg bid to a maximum dose of 300 mg bid |
| Placebo | Placebo comparator | Drug: placeboPlacebo to 4 capsules bid |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| pregabalin (Lyrica)Also: pregabalin75 mg bid to 300 mg bid based on per subject tolerability | Drug | Pregabalin (Lyrica) |
| placeboup to 4 capsules bid as tolerated | Drug | Placebo |
Primary outcome
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. .
1 secondary outcome
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Apr 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 19631949Ferrara JM, Kenney C, Davidson AL, Shinawi L, Kissel AM, Jankovic J. Efficacy and tolerability of pregabalin in essential tremor: a randomized, double-blind, placebo-controlled, crossover trial. J Neurol Sci. 2009 Oct 15;285(1-2):195-7. doi: 10.1016/j.jns.2009.06.044. Epub 2009 Jul 25.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joseph Jankovic, MD principal investigator
Baylor College of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing pregabalin (Lyrica) in people with Essential Tremor, run by Baylor College of Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Mar 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Tremor Rating Scale (TRS) Compared With Baseline. (time frame: baseline to 6 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00646451, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Apr 2021.