Trial Outcomes & Findings for Comparison of Botulinum Toxin Injections in Forearm FLexor Plus EXtensor Muscles vs. Flexor Muscles Alone for Treatment of Essential Hand Tremor(FLEX-D ET) (NCT NCT02909907)
NCT ID: NCT02909907
Last Updated: 2019-05-08
Results Overview
6 weeks post injection Clinician Global Impression if improvement Scale (CGIS) Assessment of improvement graded by the patient on a -4 to +4 scale * -4 = severe worsening * 0 = no change * +4 = complete abolishment of symptoms Higher scores represent better outcome.
COMPLETED
NA
21 participants
6 weeks
2019-05-08
Participant Flow
This was a 12-week, pilot, randomized (1:1 ratio), double-blind, placebo-controlled study of 21 patients with ET evaluated by a movement disorders specialist at the Cleveland Clinic.
Twenty-one patients were enrolled to participate, but one patient was removed from the sample due to being an extreme outlier on most outcomes of interest, and another patient dropped out after the baseline visit.
Participant milestones
| Measure |
Flexors Alone
75 units of abobotulinumtoxinA in FCR and FCU and 25 units in ECR and ECU
Botulinum toxin: Botulinum injections into dominant upper extremity using protocol outlined above.
|
Flexors Plus Extensors
150 units of abobotulinumtoxinA in flexor compartment of dominant arm (75 units in flexor carpi radialis \[FCR\] and 75 units in flexor carpi ulnaris \[FCU\]) along with placebo in extensor carpi radialis (ECR) and extensor carpi ulnaris (ECU)
Botulinum toxin: Botulinum injections into dominant upper extremity using protocol outlined above.
Placebo: Placebo injections in extensor carpi radialis (ECR) and extensor carpi ulnaris (ECU) per protocol outlined above
|
|---|---|---|
|
Overall Study
STARTED
|
10
|
10
|
|
Overall Study
COMPLETED
|
10
|
9
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
Reasons for withdrawal
| Measure |
Flexors Alone
75 units of abobotulinumtoxinA in FCR and FCU and 25 units in ECR and ECU
Botulinum toxin: Botulinum injections into dominant upper extremity using protocol outlined above.
|
Flexors Plus Extensors
150 units of abobotulinumtoxinA in flexor compartment of dominant arm (75 units in flexor carpi radialis \[FCR\] and 75 units in flexor carpi ulnaris \[FCU\]) along with placebo in extensor carpi radialis (ECR) and extensor carpi ulnaris (ECU)
Botulinum toxin: Botulinum injections into dominant upper extremity using protocol outlined above.
Placebo: Placebo injections in extensor carpi radialis (ECR) and extensor carpi ulnaris (ECU) per protocol outlined above
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
Baseline Characteristics
Comparison of Botulinum Toxin Injections in Forearm FLexor Plus EXtensor Muscles vs. Flexor Muscles Alone for Treatment of Essential Hand Tremor(FLEX-D ET)
Baseline characteristics by cohort
| Measure |
Flexors Alone
n=10 Participants
75 units of abobotulinumtoxinA in FCR and FCU and 25 units in ECR and ECU
Botulinum toxin: Botulinum injections into dominant upper extremity using protocol outlined above.
|
Flexors Plus Extensors
n=9 Participants
150 units of abobotulinumtoxinA in flexor compartment of dominant arm (75 units in flexor carpi radialis \[FCR\] and 75 units in flexor carpi ulnaris \[FCU\]) along with placebo in extensor carpi radialis (ECR) and extensor carpi ulnaris (ECU)
Botulinum toxin: Botulinum injections into dominant upper extremity using protocol outlined above.
Placebo: Placebo injections in extensor carpi radialis (ECR) and extensor carpi ulnaris (ECU) per protocol outlined above
|
Total
n=19 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
73.1 years
STANDARD_DEVIATION 12.0 • n=5 Participants
|
64.9 years
STANDARD_DEVIATION 9.1 • n=7 Participants
|
69.2 years
STANDARD_DEVIATION 11.2 • n=5 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
9 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Right-handed
|
9 participants
n=5 Participants
|
7 participants
n=7 Participants
|
16 participants
n=5 Participants
|
|
TRS mean
|
12.9 units on a scale
STANDARD_DEVIATION 4.6 • n=5 Participants
|
11.3 units on a scale
STANDARD_DEVIATION 4.1 • n=7 Participants
|
12.1 units on a scale
STANDARD_DEVIATION 4.3 • n=5 Participants
|
|
QUEST Health status self-report, med(IQR)
|
82.5 units on a scale
n=5 Participants
|
82.5 units on a scale
n=7 Participants
|
82.5 units on a scale
n=5 Participants
|
|
QUEST Quality of Life self-report, mean(SD)
|
84 units on a scale
STANDARD_DEVIATION 9.7 • n=5 Participants
|
82.8 units on a scale
STANDARD_DEVIATION 6.7 • n=7 Participants
|
83.4 units on a scale
STANDARD_DEVIATION 8.2 • n=5 Participants
|
|
QUEST Communication, med (IQR)
|
0 units on a scale
n=5 Participants
|
0 units on a scale
n=7 Participants
|
0 units on a scale
n=5 Participants
|
|
QUEST Work, med (IQR)
|
0 units on a scale
n=5 Participants
|
8.3 units on a scale
n=7 Participants
|
0 units on a scale
n=5 Participants
|
|
QUEST Hobbies, med (IQR)
|
0 units on a scale
n=5 Participants
|
0 units on a scale
n=7 Participants
|
0 units on a scale
n=5 Participants
|
|
QUEST Physical, med (IQR)
|
44.4 units on a scale
n=5 Participants
|
61.1 units on a scale
n=7 Participants
|
61.1 units on a scale
n=5 Participants
|
|
QUEST Psychosocial, med (IQR)
|
8.3 units on a scale
n=5 Participants
|
25 units on a scale
n=7 Participants
|
11.1 units on a scale
n=5 Participants
|
|
QUEST Summary Index, med (IQR)
|
12.2 units on a scale
n=5 Participants
|
26.4 units on a scale
n=7 Participants
|
17.8 units on a scale
n=5 Participants
|
|
PHQ-9, med (IQR)
|
0.5 units on a scale
n=5 Participants
|
4 units on a scale
n=7 Participants
|
2 units on a scale
n=5 Participants
|
|
GAD-7, med (IQR)
|
0 Score on a scale
n=5 Participants
|
2 Score on a scale
n=7 Participants
|
0 Score on a scale
n=5 Participants
|
|
Age of onset, med (IQR)
|
55.5 years
n=5 Participants
|
58 years
n=7 Participants
|
58 years
n=5 Participants
|
|
Disease duration, med (IQR)
|
5.5 Years
n=5 Participants
|
5 Years
n=7 Participants
|
5 Years
n=5 Participants
|
|
Main Grip Strength
|
30.8 Kg
n=5 Participants
|
28 Kg
n=7 Participants
|
29.7 Kg
n=5 Participants
|
PRIMARY outcome
Timeframe: 6 weeks6 weeks post injection Clinician Global Impression if improvement Scale (CGIS) Assessment of improvement graded by the patient on a -4 to +4 scale * -4 = severe worsening * 0 = no change * +4 = complete abolishment of symptoms Higher scores represent better outcome.
Outcome measures
| Measure |
Flexors Alone
n=10 Participants
75 units of abobotulinumtoxinA in FCR and FCU and 25 units in ECR and ECU
Botulinum toxin: Botulinum injections into dominant upper extremity using protocol outlined above.
|
Flexors Plus Extensors
n=9 Participants
150 units of abobotulinumtoxinA in flexor compartment of dominant arm (75 units in flexor carpi radialis \[FCR\] and 75 units in flexor carpi ulnaris \[FCU\]) along with placebo in extensor carpi radialis (ECR) and extensor carpi ulnaris (ECU)
Botulinum toxin: Botulinum injections into dominant upper extremity using protocol outlined above.
Placebo: Placebo injections in extensor carpi radialis (ECR) and extensor carpi ulnaris (ECU) per protocol outlined above
|
|---|---|---|
|
Difference in the 6 Week Post Injection Patient Global Impression of Improvement Scale (PGIS) Between Flexors Along and Flexors Plus Extensors Groups.
|
1.2 score on a scale
Interval 1.0 to 3.0
|
2.2 score on a scale
Interval 1.6 to 4.0
|
SECONDARY outcome
Timeframe: Baseline and 6 weeksTRS: Tremor Rating Scale : scale composed of 6 items rated from 0-4. 0=none/normal and 4 = very severe/high level of disability. Total score is the sum of all items. Max score 24 ( maximal severity of tremor) Minimal score 0= no tremor/normal.
Outcome measures
| Measure |
Flexors Alone
n=10 Participants
75 units of abobotulinumtoxinA in FCR and FCU and 25 units in ECR and ECU
Botulinum toxin: Botulinum injections into dominant upper extremity using protocol outlined above.
|
Flexors Plus Extensors
n=9 Participants
150 units of abobotulinumtoxinA in flexor compartment of dominant arm (75 units in flexor carpi radialis \[FCR\] and 75 units in flexor carpi ulnaris \[FCU\]) along with placebo in extensor carpi radialis (ECR) and extensor carpi ulnaris (ECU)
Botulinum toxin: Botulinum injections into dominant upper extremity using protocol outlined above.
Placebo: Placebo injections in extensor carpi radialis (ECR) and extensor carpi ulnaris (ECU) per protocol outlined above
|
|---|---|---|
|
Difference in Tremor Rating Scale Score (TSR)Change From Baseline to Week 6 Between Flexors Alone and Flexors Plus Extensors Groups.
|
-5 score on a scale
Interval -6.0 to -4.0
|
-5 score on a scale
Interval -6.0 to -4.0
|
SECONDARY outcome
Timeframe: 6 weeks6 weeks post injection Clinician Global Impression if improvement Scale (CGIS) Assessment of improvement graded by clinician on a -4 to +4 scale * -4 = severe worsening * 0 = no change * +4 = complete abolishment of symptoms Higher scores represent better outcome.
Outcome measures
| Measure |
Flexors Alone
n=10 Participants
75 units of abobotulinumtoxinA in FCR and FCU and 25 units in ECR and ECU
Botulinum toxin: Botulinum injections into dominant upper extremity using protocol outlined above.
|
Flexors Plus Extensors
n=9 Participants
150 units of abobotulinumtoxinA in flexor compartment of dominant arm (75 units in flexor carpi radialis \[FCR\] and 75 units in flexor carpi ulnaris \[FCU\]) along with placebo in extensor carpi radialis (ECR) and extensor carpi ulnaris (ECU)
Botulinum toxin: Botulinum injections into dominant upper extremity using protocol outlined above.
Placebo: Placebo injections in extensor carpi radialis (ECR) and extensor carpi ulnaris (ECU) per protocol outlined above
|
|---|---|---|
|
Difference in the 6 Week Post Injection Clinician Global Impression of Improvement Scale (CGIS) Between Flexors Along and Flexors Plus Extensors Groups.
|
1 score on a scale
Interval 0.0 to 2.0
|
3 score on a scale
Interval 1.0 to 3.0
|
SECONDARY outcome
Timeframe: Baseline and 6 weeksQUEST( Quality of Life in Essential Tremor Questionnaire ) is a 30-item, ET-specific quality of life scale . Items contribute to five dimensions. Physical/ADL (9 items ), Psychosocial (9 items), Communication (3 items), Hobbies/Leisure (3 items), and Work/Finances (6 items). The score on each scale is expressed as a percentage of the total score possible, with a higher score indicating greater dissatisfaction with that domain of QOL. A total or summary index corresponds to the mean of the five domain scores. The total summary index corresponds to the mean of the five domain scores. Maximal score 100: worse quality of life. Minimal Score 0: best quality of life. This outcome represents the median of the differences between baseline and week 6 in QUEST summary index.Positive index change values indicate that the score increased and negative values indicate that the score decreased.
Outcome measures
| Measure |
Flexors Alone
n=10 Participants
75 units of abobotulinumtoxinA in FCR and FCU and 25 units in ECR and ECU
Botulinum toxin: Botulinum injections into dominant upper extremity using protocol outlined above.
|
Flexors Plus Extensors
n=9 Participants
150 units of abobotulinumtoxinA in flexor compartment of dominant arm (75 units in flexor carpi radialis \[FCR\] and 75 units in flexor carpi ulnaris \[FCU\]) along with placebo in extensor carpi radialis (ECR) and extensor carpi ulnaris (ECU)
Botulinum toxin: Botulinum injections into dominant upper extremity using protocol outlined above.
Placebo: Placebo injections in extensor carpi radialis (ECR) and extensor carpi ulnaris (ECU) per protocol outlined above
|
|---|---|---|
|
Difference of the Quality of Life in Essential Tremor Questionnaire (QUEST) Summary Index Change at Week 6 Compared to Baseline Between Wrist Flexors Versus Wrist Flexors Plus Extensors Group.
|
1.1 score on a scale
Interval -1.7 to 5.6
|
-5.3 score on a scale
Interval -6.11 to 1.1
|
SECONDARY outcome
Timeframe: 6 weeksthe median of the differences in grip strength between baseline and week 6, A negative value indicates a decrease in grip strength in Kg at week 6.
Outcome measures
| Measure |
Flexors Alone
n=10 Participants
75 units of abobotulinumtoxinA in FCR and FCU and 25 units in ECR and ECU
Botulinum toxin: Botulinum injections into dominant upper extremity using protocol outlined above.
|
Flexors Plus Extensors
n=9 Participants
150 units of abobotulinumtoxinA in flexor compartment of dominant arm (75 units in flexor carpi radialis \[FCR\] and 75 units in flexor carpi ulnaris \[FCU\]) along with placebo in extensor carpi radialis (ECR) and extensor carpi ulnaris (ECU)
Botulinum toxin: Botulinum injections into dominant upper extremity using protocol outlined above.
Placebo: Placebo injections in extensor carpi radialis (ECR) and extensor carpi ulnaris (ECU) per protocol outlined above
|
|---|---|---|
|
Difference in the Post Injection Grip Strength Change Between Flexor Only Group and Flexor and Extensors Group at 6 Weeks.
|
-6.2 Kilograms
Interval -15.3 to -5.3
|
-11 Kilograms
Interval -13.3 to 7.3
|
SECONDARY outcome
Timeframe: 12 weeksTRS: Tremor Rating Scale : scale composed of 6 items rated from 0-4. 0=none or normal and 4 = very severe or high level of disability. Total score is the sum of all items. Max score 24 ( maximal severity of tremor) Minimal score 0= no tremor/normal.
Outcome measures
| Measure |
Flexors Alone
n=10 Participants
75 units of abobotulinumtoxinA in FCR and FCU and 25 units in ECR and ECU
Botulinum toxin: Botulinum injections into dominant upper extremity using protocol outlined above.
|
Flexors Plus Extensors
n=9 Participants
150 units of abobotulinumtoxinA in flexor compartment of dominant arm (75 units in flexor carpi radialis \[FCR\] and 75 units in flexor carpi ulnaris \[FCU\]) along with placebo in extensor carpi radialis (ECR) and extensor carpi ulnaris (ECU)
Botulinum toxin: Botulinum injections into dominant upper extremity using protocol outlined above.
Placebo: Placebo injections in extensor carpi radialis (ECR) and extensor carpi ulnaris (ECU) per protocol outlined above
|
|---|---|---|
|
12 Weeks Post Injection Tremor Rating Scale for Flexors Group and Flexors Plus Extensors Group.
|
6 score on a scale
Interval 6.0 to 9.0
|
6 score on a scale
Interval 3.0 to 12.0
|
SECONDARY outcome
Timeframe: 12 weeks12 week post injection in Clinician Global Impression Scale-Improvement Subscale (CGIS) Assessment of improvement graded by the clinician on a -4 to +4 scale * -4 = severe worsening * 0 = no change * +4 = complete abolishment of symptoms Higher scores represent better outcome.
Outcome measures
| Measure |
Flexors Alone
n=10 Participants
75 units of abobotulinumtoxinA in FCR and FCU and 25 units in ECR and ECU
Botulinum toxin: Botulinum injections into dominant upper extremity using protocol outlined above.
|
Flexors Plus Extensors
n=9 Participants
150 units of abobotulinumtoxinA in flexor compartment of dominant arm (75 units in flexor carpi radialis \[FCR\] and 75 units in flexor carpi ulnaris \[FCU\]) along with placebo in extensor carpi radialis (ECR) and extensor carpi ulnaris (ECU)
Botulinum toxin: Botulinum injections into dominant upper extremity using protocol outlined above.
Placebo: Placebo injections in extensor carpi radialis (ECR) and extensor carpi ulnaris (ECU) per protocol outlined above
|
|---|---|---|
|
12 Week Post Injection in Clinician Global Impression Scale-Improvement Subscale (CGIS)
|
3 score on a scale
Interval 1.0 to 3.0
|
3 score on a scale
Interval 1.0 to 3.0
|
SECONDARY outcome
Timeframe: 12 weeksPatient Global Impression Scale-Improvement Subscale (PGIS) Assessment of improvement graded by patient on a -4 to +4 scale * -4 = severe worsening * 0 = no change * +4 = complete abolishment of symptoms Higher scores represent better outcome.
Outcome measures
| Measure |
Flexors Alone
n=10 Participants
75 units of abobotulinumtoxinA in FCR and FCU and 25 units in ECR and ECU
Botulinum toxin: Botulinum injections into dominant upper extremity using protocol outlined above.
|
Flexors Plus Extensors
n=9 Participants
150 units of abobotulinumtoxinA in flexor compartment of dominant arm (75 units in flexor carpi radialis \[FCR\] and 75 units in flexor carpi ulnaris \[FCU\]) along with placebo in extensor carpi radialis (ECR) and extensor carpi ulnaris (ECU)
Botulinum toxin: Botulinum injections into dominant upper extremity using protocol outlined above.
Placebo: Placebo injections in extensor carpi radialis (ECR) and extensor carpi ulnaris (ECU) per protocol outlined above
|
|---|---|---|
|
12 Week Post Injection Patient Global Impression Scale-Improvement Subscale (PGIS)
|
1 score on a scale
Interval 1.0 to 3.0
|
3 score on a scale
Interval 1.0 to 3.0
|
SECONDARY outcome
Timeframe: Baseline and 12 weeks.QUEST( Quality of Life in Essential Tremor Questionnaire ) is a 30-item, ET-specific quality of life scale . Items contribute to five dimensions. Physical/ADL (9 items ), Psychosocial (9 items), Communication (3 items), Hobbies/Leisure (3 items), and Work/Finances (6 items). The score on each scale is expressed as a percentage of the total score possible, with a higher score indicating greater dissatisfaction with that domain of QOL. A total or summary index corresponds to the mean of the five domain scores. The total summary index corresponds to the mean of the five domain scores. Maximal score 100: worse quality of life. Minimal Score 0: best quality of life. This outcome represents the median of the differences between baseline and week 6 in QUEST summary index. Positive index change values indicate that the score increased and negative values indicate that the score decreased.
Outcome measures
| Measure |
Flexors Alone
n=10 Participants
75 units of abobotulinumtoxinA in FCR and FCU and 25 units in ECR and ECU
Botulinum toxin: Botulinum injections into dominant upper extremity using protocol outlined above.
|
Flexors Plus Extensors
n=9 Participants
150 units of abobotulinumtoxinA in flexor compartment of dominant arm (75 units in flexor carpi radialis \[FCR\] and 75 units in flexor carpi ulnaris \[FCU\]) along with placebo in extensor carpi radialis (ECR) and extensor carpi ulnaris (ECU)
Botulinum toxin: Botulinum injections into dominant upper extremity using protocol outlined above.
Placebo: Placebo injections in extensor carpi radialis (ECR) and extensor carpi ulnaris (ECU) per protocol outlined above
|
|---|---|---|
|
Difference of Quality of Life in Essential Tremor Questionnaire (QUEST) Summary Index Change at Week 12 Compared to Baseline Between Wrist Flexors Versus Wrist Flexors Plus Extensors Group.
|
-1.67 score on a scale
Interval -3.9 to -0.56
|
0 score on a scale
Interval -6.11 to 6.67
|
Adverse Events
Flexors Alone
Flexors Plus Extensors
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Flexors Alone
n=10 participants at risk
75 units of abobotulinumtoxinA in FCR and FCU and 25 units in ECR and ECU
Botulinum toxin: Botulinum injections into dominant upper extremity using protocol outlined above.
|
Flexors Plus Extensors
n=9 participants at risk
150 units of abobotulinumtoxinA in flexor compartment of dominant arm (75 units in flexor carpi radialis \[FCR\] and 75 units in flexor carpi ulnaris \[FCU\]) along with placebo in extensor carpi radialis (ECR) and extensor carpi ulnaris (ECU)
Botulinum toxin: Botulinum injections into dominant upper extremity using protocol outlined above.
Placebo: Placebo injections in extensor carpi radialis (ECR) and extensor carpi ulnaris (ECU) per protocol outlined above
|
|---|---|---|
|
Nervous system disorders
Finger Weakness
|
40.0%
4/10 • 12 weeks
|
55.6%
5/9 • 12 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place