TremorPhase 2NCT02427646
Kinematic-guided BoNT-A Treatment for ET and PD Tremor
A Phase 2 study testing BoNT-A in people with Tremor, run by Western University, Canada.
Trial summary
The present study attempts to fill a critical knowledge gap of BoNT A in tremor management by studying the efficacy of IncobotulinumtoxinA (Xeomin®) injection for hand tremor in essential tremor and idiopathic Parkinson disease using data regarding composition of tremor obtained through sophisticated, yet clinically… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Tremor
- What is being tested?
- BoNT-A
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- No sites listed yet
- Study dates
- Oct 2011to Jun 2020
- Phase
- Phase 2
- 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
- Consenting male and female participants, aged 18 years to 80 years
- PD individuals diagnosed by UK Brain Bank Criteria with stage H\&Y2-3 disease or ET with hand tremor in their motor dominant hand
- Stable IPD/ET medication management for the 6 month duration prior to their enrollment in the study
- Individuals with IPD will be eligible for the study only if tremor is their primary and most bothersome symptom as determined by clinical exam and patient report
- Participants who are botulinum toxin naïve for tremor management
Who cannot join
- History of stroke
- Muscle weakness or any related compartmental muscle syndrome
- Smoking
- Offending medications (Lithium, valproate, steroids, amiodarone, beta-adrenergic agonists (e.g. salbutamol))
- Contradictions per the Xeomin® drug monograph
- Patients prescribed zonisamide
About this study
Official title: Use of Kinematic Assessment of Hand Tremor Pre- and Post- Treatment With Botulinum Toxin Type A in Essential Tremor and Parkinson Disease
The present study attempts to fill a critical knowledge gap of BoNT A in tremor management by studying the efficacy of IncobotulinumtoxinA (Xeomin®) injection for hand tremor in essential tremor and idiopathic Parkinson disease using data regarding composition of tremor obtained through sophisticated, yet clinically accessible multi-sensor based kinematic information.
Read the detailed description
Current pharmacological agents used to treat Parkinson disease (PD) tremor and essential tremor (ET) provide suboptimal benefit and are commonly associated with significant adverse effects. Botulinum toxin type A (BoNT-A) has been shown to be effective for wrist tremor though functionally bothersome muscle weakness frequently occurs. This is the longest study to date demonstrating that BoNT-A therapy coupled with kinematic guidance can provide efficacious outcomes for upper limb tremor with minimized unwanted weakness. A total of 28 PD and 24 ET participants with bothersome, disabling tremor, received six serial BoNT-A treatments every 16 weeks starting at week 0 with a follow-up visit 6 weeks following a treatment, totaling 96 weeks. Clinical scales, including Fahn-Tolosa-Marin tremor rating scale (FTM), and sensor-based tremor assessments were conducted at each visit. Kinematics was utilized to identify which arm muscles contributed to the tremulous movements and the experienced injector used clinical expertise in determining BoNT-A dosages. Following BoNT-A treatment, clinical ratings of tremor severity and functional ability (FTM) showed significant improvements following the first treatment which was maintained up to week 96 in PD and ET. Kinematics detected a significant reduction in PD and ET tremor amplitudes by 70% and 76% over the treatment course, respectively. By objectively distinguishing tremulous muscles and tremor severity, adverse effects were limited to mild perceived weakness by participants in injected muscles during follow-ups. Following the fourth treatment, BoNT-A dosages in flexor and extensor wrist muscles and biceps were reduced for those experiencing residual weakness which ultimately did not interfere with tremor relief or arm function. Kinematics is an objective method that can aid clinicians in assessing and determining optimal BoNT-A parameters to alleviate both PD and ET tremor. BoNT-A injections are tolerable and effective when focal therapy regimens are determined and optimized kinematically over a long-term
- Conditions
- Tremor
- Being tested
- BoNT-A
- Keywords
- Kinematics, Botulinum toxin type A
- Medical subject headings
- Tremor
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BoNT-ADrug
Also called Botulinum neurotoxin type A, IncobotulinumtoxinA
A serotype of botulinum toxins that has specificity for cleavage of SYNAPTOSOMAL-ASSOCIATED PROTEIN 25 (SNAP-25). BoNT-A's pharmacological action is to inhibit the release of acetylcholine from the neuromuscular junction. BoNT-A peripherally applied using optimal parameters by intramuscular injections to treat tremor in the most bothersome upper extremity every 16 weeks over 96 weeks. The study will be extended for those participants who benefited and will receive treatment every 12 weeks over 96 weeks. BoNT-A dose will range from 50-300 U per arm.
| Study group | Role | What they receive |
|---|---|---|
| ET BoNT-A treatment | Experimental | ET participants treated with kinematic-guided BoNT-A injections over 6 injection cycles Receives: Drug: BoNT-A |
| PD tremor BoNT-A treatment | Experimental | PD participants treated with kinematic-guided BoNT-A injections over 6 injection cycles Receives: Drug: BoNT-A |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Tremor Rating Scale (Fahn-Tolosa-Marin Tremor Rating Scale)
Improvement in hand tremor as determined by a reduction of >8 points on a standardized clinical assessment tool (Fahn-Tolosa-Marin Tremor Assessment Scale) pre and post Xeomin® injection using kinematic guided injection parameters for both IPD and ET. Lower scores indicate a better outcome. Means and standard deviations are provided in the data tables. FTM minimum and maximum scores range from 0 to 92 FTM points.
Measured: 0 to 96 weeks
Secondary outcomes (1)
Kinematic Tremor Severity
For two subgroups of participants: (A) those with a > 8 point improvement on the tremor rating scale and (B) those with a change ≤ 8 points on the tremor rating scale, Group A will have 50% reduction in overall tremor amplitude as measured by kinematics. Kinematic measures were graphically represented as mean angular RMS amplitude and standard deviations of the population at the wrist over three trials during scripted task. Kinematic tremor analysis is shown in angular root mean square (RMS) amplitudes
Measured: 96 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Apr 2015 (estimated)
- Study startOct 2011
- Primary completionApr 2015
- Study completionJun 2020 (estimated)
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 (9)Papers the sponsor has linked to this study.
- Other trials for TremorStudies of the same condition, open and under way.
- More trials run by Western University, CanadaThe 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
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Lead sponsor
- Western University, Canada
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mandar Jog, Western University, Canada
- Investigators
- Mandar Jog, MD, FRCPC, Principal investigator, Clinical Neurological Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02427646
- Sponsor's protocol ID
- 18445
- Status last verified
- Aug 2019
- First submitted
- 22 Apr 2015
- Last updated
- 20 Aug 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Schantz EJ, Johnson EA. Properties and use of botulinum toxin and other microbial neurotoxins in medicine. Microbiol Rev. 1992 Mar;56(1):80-99. doi: 10.1128/mr.56.1.80-99.1992.
PubMed 1579114Evidente VG, Adler CH. An update on the neurologic applications of botulinum toxins. Curr Neurol Neurosci Rep. 2010 Sep;10(5):338-44. doi: 10.1007/s11910-010-0129-z.
PubMed 20567945Benito-Leon J, Louis ED. Essential tremor: emerging views of a common disorder. Nat Clin Pract Neurol. 2006 Dec;2(12):666-78; quiz 2p following 691. doi: 10.1038/ncpneuro0347.
PubMed 17117170Pullman SL, Elibol B, Fahn S. Modulation of parkinsonian tremor by radial nerve palsy. Neurology. 1994 Oct;44(10):1861-4. doi: 10.1212/wnl.44.10.1861.
PubMed 7936237Jankovic J, Schwartz K, Clemence W, Aswad A, Mordaunt J. A randomized, double-blind, placebo-controlled study to evaluate botulinum toxin type A in essential hand tremor. Mov Disord. 1996 May;11(3):250-6. doi: 10.1002/mds.870110306.
PubMed 8723140Brin MF, Lyons KE, Doucette J, Adler CH, Caviness JN, Comella CL, Dubinsky RM, Friedman JH, Manyam BV, Matsumoto JY, Pullman SL, Rajput AH, Sethi KD, Tanner C, Koller WC. A randomized, double masked, controlled trial of botulinum toxin type A in essential hand tremor. Neurology. 2001 Jun 12;56(11):1523-8. doi: 10.1212/wnl.56.11.1523.
PubMed 11402109Wissel J, Masuhr F, Schelosky L, Ebersbach G, Poewe W. Quantitative assessment of botulinum toxin treatment in 43 patients with head tremor. Mov Disord. 1997 Sep;12(5):722-6. doi: 10.1002/mds.870120516.
PubMed 9380055Trosch RM, Pullman SL. Botulinum toxin A injections for the treatment of hand tremors. Mov Disord. 1994 Nov;9(6):601-9. doi: 10.1002/mds.870090604.
PubMed 7845399Samotus O, Rahimi F, Lee J, Jog M. Functional Ability Improved in Essential Tremor by IncobotulinumtoxinA Injections Using Kinematically Determined Biomechanical Patterns - A New Future. PLoS One. 2016 Apr 21;11(4):e0153739. doi: 10.1371/journal.pone.0153739. eCollection 2016.
PubMed 27101283
Study at a glance
From the registry record, last updated by the sponsor on 20 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Use of Kinematic Assessment of Hand Tremor Pre- and Post- Treatment With Botulinum Toxin Type A in Essential Tremor and Parkinson Disease
- ClinicalTrials.gov ID
- NCT02427646
- Acronym / sponsor ID
- 18445
- Conditions
- Tremor
- Keywords
- Kinematics, Botulinum toxin type A
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 54 participants (actual)
- Lead sponsor
- Western University, CanadaUniversity, hospital or other
- Study start
- Oct 2011 (actual)
- Primary completion
- Apr 2015 (actual)
- Study completion
- Jun 2020 (estimated)
- First posted
- 28 Apr 2015 (estimated)
- Results
- Posted 20 Aug 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The present study attempts to fill a critical knowledge gap of BoNT A in tremor management by studying the efficacy of IncobotulinumtoxinA (Xeomin®) injection for hand tremor in essential tremor and idiopathic Parkinson disease using data regarding composition of tremor obtained through sophisticated, yet clinically accessible multi-sensor based kinematic information.
Detailed description
Current pharmacological agents used to treat Parkinson disease (PD) tremor and essential tremor (ET) provide suboptimal benefit and are commonly associated with significant adverse effects. Botulinum toxin type A (BoNT-A) has been shown to be effective for wrist tremor though functionally bothersome muscle weakness frequently occurs. This is the longest study to date demonstrating that BoNT-A therapy coupled with kinematic guidance can provide efficacious outcomes for upper limb tremor with minimized unwanted weakness. A total of 28 PD and 24 ET participants with bothersome, disabling tremor, received six serial BoNT-A treatments every 16 weeks starting at week 0 with a follow-up visit 6 weeks following a treatment, totaling 96 weeks. Clinical scales, including Fahn-Tolosa-Marin tremor rating scale (FTM), and sensor-based tremor assessments were conducted at each visit. Kinematics was utilized to identify which arm muscles contributed to the tremulous movements and the experienced injector used clinical expertise in determining BoNT-A dosages. Following BoNT-A treatment, clinical ratings of tremor severity and functional ability (FTM) showed significant improvements following the first treatment which was maintained up to week 96 in PD and ET. Kinematics detected a significant reduction in PD and ET tremor amplitudes by 70% and 76% over the treatment course, respectively. By objectively distinguishing tremulous muscles and tremor severity, adverse effects were limited to mild perceived weakness by participants in injected muscles during follow-ups. Following the fourth treatment, BoNT-A dosages in flexor and extensor wrist muscles and biceps were reduced for those experiencing residual weakness which ultimately did not interfere with tremor relief or arm function. Kinematics is an objective method that can aid clinicians in assessing and determining optimal BoNT-A parameters to alleviate both PD and ET tremor. BoNT-A injections are tolerable and effective when focal therapy regimens are determined and optimized kinematically over a long-term
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ET BoNT-A treatment | Experimental | Drug: BoNT-AET participants treated with kinematic-guided BoNT-A injections over 6 injection cycles |
| PD tremor BoNT-A treatment | Experimental | Drug: BoNT-APD participants treated with kinematic-guided BoNT-A injections over 6 injection cycles |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Consenting male and female participants, aged 18 years to 80 years
- PD individuals diagnosed by UK Brain Bank Criteria with stage H\&Y2-3 disease or ET with hand tremor in their motor dominant hand
- Stable IPD/ET medication management for the 6 month duration prior to their enrollment in the study
- Individuals with IPD will be eligible for the study only if tremor is their primary and most bothersome symptom as determined by clinical exam and patient report
- Participants who are botulinum toxin naïve for tremor management
Key exclusion criteria (6 listed)
- History of stroke
- Muscle weakness or any related compartmental muscle syndrome
- Smoking
- Offending medications (Lithium, valproate, steroids, amiodarone, beta-adrenergic agonists (e.g. salbutamol))
- Contradictions per the Xeomin® drug monograph
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 |
|---|---|---|
| BoNT-AAlso: Botulinum neurotoxin type A, IncobotulinumtoxinAA serotype of botulinum toxins that has specificity for cleavage of SYNAPTOSOMAL-ASSOCIATED PROTEIN 25 (SNAP-25). BoNT-A's pharmacological action is to inhibit the release of acetylcholine from the neuromuscular junction. BoNT-A peripherally applied using optimal parameters by intramuscular injections to treat tremor in the most bothersome upper extremity every 16 weeks over 96 weeks. The study will be extended for those participants who benefited and will receive treatment every 12 weeks over 96 weeks. BoNT-A dose will range from 50-300 U per arm. | Drug | ET BoNT-A treatment, PD tremor BoNT-A treatment |
Primary outcome
Clinical Tremor Rating Scale (Fahn-Tolosa-Marin Tremor Rating Scale)
Time frame: 0 to 96 weeks
Improvement in hand tremor as determined by a reduction of >8 points on a standardized clinical assessment tool (Fahn-Tolosa-Marin Tremor Assessment Scale) pre and post Xeomin® injection using kinematic guided injection parameters for both IPD and ET. Lower scores indicate a better outcome. Means and standard deviations are provided in the data tables. FTM minimum and maximum scores range from 0 to 92 FTM points.
1 secondary outcome
Kinematic Tremor Severity
Time frame: 96 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Aug 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 1579114Schantz EJ, Johnson EA. Properties and use of botulinum toxin and other microbial neurotoxins in medicine. Microbiol Rev. 1992 Mar;56(1):80-99. doi: 10.1128/mr.56.1.80-99.1992.
- Background: PubMed 20567945Evidente VG, Adler CH. An update on the neurologic applications of botulinum toxins. Curr Neurol Neurosci Rep. 2010 Sep;10(5):338-44. doi: 10.1007/s11910-010-0129-z.
- Background: PubMed 17117170Benito-Leon J, Louis ED. Essential tremor: emerging views of a common disorder. Nat Clin Pract Neurol. 2006 Dec;2(12):666-78; quiz 2p following 691. doi: 10.1038/ncpneuro0347.
- Background: PubMed 7936237Pullman SL, Elibol B, Fahn S. Modulation of parkinsonian tremor by radial nerve palsy. Neurology. 1994 Oct;44(10):1861-4. doi: 10.1212/wnl.44.10.1861.
- Background: PubMed 8723140Jankovic J, Schwartz K, Clemence W, Aswad A, Mordaunt J. A randomized, double-blind, placebo-controlled study to evaluate botulinum toxin type A in essential hand tremor. Mov Disord. 1996 May;11(3):250-6. doi: 10.1002/mds.870110306.
- Background: PubMed 11402109Brin MF, Lyons KE, Doucette J, Adler CH, Caviness JN, Comella CL, Dubinsky RM, Friedman JH, Manyam BV, Matsumoto JY, Pullman SL, Rajput AH, Sethi KD, Tanner C, Koller WC. A randomized, double masked, controlled trial of botulinum toxin type A in essential hand tremor. Neurology. 2001 Jun 12;56(11):1523-8. doi: 10.1212/wnl.56.11.1523.
- Background: PubMed 9380055Wissel J, Masuhr F, Schelosky L, Ebersbach G, Poewe W. Quantitative assessment of botulinum toxin treatment in 43 patients with head tremor. Mov Disord. 1997 Sep;12(5):722-6. doi: 10.1002/mds.870120516.
- Background: PubMed 7845399Trosch RM, Pullman SL. Botulinum toxin A injections for the treatment of hand tremors. Mov Disord. 1994 Nov;9(6):601-9. doi: 10.1002/mds.870090604.
- Derived from this study: PubMed 27101283Samotus O, Rahimi F, Lee J, Jog M. Functional Ability Improved in Essential Tremor by IncobotulinumtoxinA Injections Using Kinematically Determined Biomechanical Patterns - A New Future. PLoS One. 2016 Apr 21;11(4):e0153739. doi: 10.1371/journal.pone.0153739. eCollection 2016.
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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.
Mandar Jog, MD, FRCPC principal investigator
Clinical Neurological Sciences
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing BoNT-A in people with Tremor, run by Western University, Canada.
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 5 inclusion and 6 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: status not confirmed, as of the sponsor's last update on 20 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. 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?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 20 Aug 2019). 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?
Clinical Tremor Rating Scale (Fahn-Tolosa-Marin Tremor Rating Scale) (time frame: 0 to 96 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 NCT02427646, which also lists 9 linked publications.
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 20 Aug 2019.