Trial Outcomes & Findings for Neurotoxin and Physical Therapy (NCT NCT02177617)

NCT ID: NCT02177617

Last Updated: 2023-08-02

Results Overview

The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) is a measure of symptoms, pain, and disability related to Cervical Dystonia. The total TWSTRS scale includes a global outcome score (total score) and scores on each of 3 subscales for severity (0-35), disability (0-30), and pain (0-20), which are summed together for a total score (0-85), with higher scores indicating greater impairment. The TWSTRS is completed by a neurologist who visually assesses the patient's symptoms, and asks the patient to self-report on pain and disability.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 16 participants
• Primary outcome timeframe: absolute value at Week 12
• Results posted on: 2023-08-02

Participant Flow

Participant milestones

Measure	Botox Only Participants randomized to receive Botox injections alone. Botox injection: Participants will receive a tailored dose of Botox to address their Cervical Dystonia symptoms Transcranial magnetic stimulation (TMS): For these tests, participants will sit in a chair that looks like one found at the dentist's office. A nerve stimulator will be placed on the wrist of the right hand to stimulate the median and ulnar nerves. The intensity of the nerve stimulator will be gradually increased until the right thumb begins to twitch. A magnetic coil will be placed on the scalp on the left side of the head, overlying the brain's motor cortex, to stimulate the brain's output to the muscles in the opposite hand. This procedure will be repeated using the left wrist and the right side of the head.	Botox Plus Physical Therapy Participants randomized to receive Botox injection combined with Physical Therapy Botox injection: Participants will receive a tailored dose of Botox to address their Cervical Dystonia symptoms Physical Therapy: Participants will undergo physical therapy sessions with a physical therapist trained in movement disorders. Participants will be instructed to continue these exercises five times per week, and will be called weekly by the investigator to check progress. Transcranial magnetic stimulation (TMS): For these tests, participants will sit in a chair that looks like one found at the dentist's office. A nerve stimulator will be placed on the wrist of the right hand to stimulate the median and ulnar nerves. The intensity of the nerve stimulator will be gradually increased until the right thumb begins to twitch. A magnetic coil will be placed on the scalp on the left side of the head, overlying the brain's motor cortex, to stimulate the brain's output to the muscles in the opposite hand. This procedure will be repeated using the left wrist and the right side of the head.
Overall Study STARTED	8	8
Overall Study COMPLETED	8	8
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Neurotoxin and Physical Therapy

Baseline characteristics by cohort

Measure	Botox Only n=8 Participants Participants randomized to receive Botox injections alone. Botox injection: Participants will receive a tailored dose of Botox to address their Cervical Dystonia symptoms Transcranial magnetic stimulation (TMS): For these tests, participants will sit in a chair that looks like one found at the dentist's office. A nerve stimulator will be placed on the wrist of the right hand to stimulate the median and ulnar nerves. The intensity of the nerve stimulator will be gradually increased until the right thumb begins to twitch. A magnetic coil will be placed on the scalp on the left side of the head, overlying the brain's motor cortex, to stimulate the brain's output to the muscles in the opposite hand. This procedure will be repeated using the left wrist and the right side of the head.	Botox Plus Physical Therapy n=8 Participants Participants randomized to receive Botox injection combined with Physical Therapy Botox injection: Participants will receive a tailored dose of Botox to address their Cervical Dystonia symptoms Physical Therapy: Participants will undergo physical therapy sessions with a physical therapist trained in movement disorders. Participants will be instructed to continue these exercises five times per week, and will be called weekly by the investigator to check progress. Transcranial magnetic stimulation (TMS): For these tests, participants will sit in a chair that looks like one found at the dentist's office. A nerve stimulator will be placed on the wrist of the right hand to stimulate the median and ulnar nerves. The intensity of the nerve stimulator will be gradually increased until the right thumb begins to twitch. A magnetic coil will be placed on the scalp on the left side of the head, overlying the brain's motor cortex, to stimulate the brain's output to the muscles in the opposite hand. This procedure will be repeated using the left wrist and the right side of the head.	Total n=16 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Age, Categorical >=65 years	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants
Age, Continuous	64.3 years STANDARD_DEVIATION 5.2 • n=5 Participants	64.7 years STANDARD_DEVIATION 5.4 • n=7 Participants	64.5 years STANDARD_DEVIATION 5.5 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Region of Enrollment United States	8 participants n=5 Participants	8 participants n=7 Participants	16 participants n=5 Participants
TWSTRS pain	4 units on a scale STANDARD_DEVIATION 1.4 • n=5 Participants	3.8 units on a scale STANDARD_DEVIATION 1.5 • n=7 Participants	3.8 units on a scale STANDARD_DEVIATION 1.2 • n=5 Participants

PRIMARY outcome

Timeframe: absolute value at Week 12

Population: mean difference between two groups was calculated

The Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) is a measure of symptoms, pain, and disability related to Cervical Dystonia. The total TWSTRS scale includes a global outcome score (total score) and scores on each of 3 subscales for severity (0-35), disability (0-30), and pain (0-20), which are summed together for a total score (0-85), with higher scores indicating greater impairment. The TWSTRS is completed by a neurologist who visually assesses the patient's symptoms, and asks the patient to self-report on pain and disability.

Outcome measures

Measure	Botox Only n=8 Participants Participants randomized to receive Botox injections alone. Botox injection: Participants will receive a tailored dose of Botox to address their Cervical Dystonia symptoms Transcranial magnetic stimulation (TMS): For these tests, participants will sit in a chair that looks like one found at the dentist's office. A nerve stimulator will be placed on the wrist of the right hand to stimulate the median and ulnar nerves. The intensity of the nerve stimulator will be gradually increased until the right thumb begins to twitch. A magnetic coil will be placed on the scalp on the left side of the head, overlying the brain's motor cortex, to stimulate the brain's output to the muscles in the opposite hand. This procedure will be repeated using the left wrist and the right side of the head.	Botox Plus Physical Therapy n=8 Participants Participants randomized to receive Botox injection combined with Physical Therapy Botox injection: Participants will receive a tailored dose of Botox to address their Cervical Dystonia symptoms Physical Therapy: Participants will undergo physical therapy sessions with a physical therapist trained in movement disorders. Participants will be instructed to continue these exercises five times per week, and will be called weekly by the investigator to check progress. Transcranial magnetic stimulation (TMS): For these tests, participants will sit in a chair that looks like one found at the dentist's office. A nerve stimulator will be placed on the wrist of the right hand to stimulate the median and ulnar nerves. The intensity of the nerve stimulator will be gradually increased until the right thumb begins to twitch. A magnetic coil will be placed on the scalp on the left side of the head, overlying the brain's motor cortex, to stimulate the brain's output to the muscles in the opposite hand. This procedure will be repeated using the left wrist and the right side of the head.
Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)	28 total score on a scale Standard Deviation 10.2	20.1 total score on a scale Standard Deviation 9.8

PRIMARY outcome

Timeframe: absolute value at Week 12

Population: mean difference between two groups calculated

The Short Form 36-Item Health Scale (SF-36) is a health survey with 36 questions that is self-reported by the study participant. It contains 8 subscales, one of which is Physical Functioning, calculated from 10 of the 36 questions. Different questions have different score ranges and valences. Therefore, their response for each question is linearly transformed to a value of 0-100 (for example, choosing response 3 on a scale of 1-5 is transformed to 60). These ten values are then averaged to generate the Physical Functioning subscore, ranging from 0-100. The higher the response value and the subscore, the higher degree of physical functioning.

More details on RAND SF-36 scoring here: https://www.rand.org/health-care/surveys_tools/mos/36-item-short-form/scoring.html

Outcome measures

Measure	Botox Only n=8 Participants Participants randomized to receive Botox injections alone. Botox injection: Participants will receive a tailored dose of Botox to address their Cervical Dystonia symptoms Transcranial magnetic stimulation (TMS): For these tests, participants will sit in a chair that looks like one found at the dentist's office. A nerve stimulator will be placed on the wrist of the right hand to stimulate the median and ulnar nerves. The intensity of the nerve stimulator will be gradually increased until the right thumb begins to twitch. A magnetic coil will be placed on the scalp on the left side of the head, overlying the brain's motor cortex, to stimulate the brain's output to the muscles in the opposite hand. This procedure will be repeated using the left wrist and the right side of the head.	Botox Plus Physical Therapy n=8 Participants Participants randomized to receive Botox injection combined with Physical Therapy Botox injection: Participants will receive a tailored dose of Botox to address their Cervical Dystonia symptoms Physical Therapy: Participants will undergo physical therapy sessions with a physical therapist trained in movement disorders. Participants will be instructed to continue these exercises five times per week, and will be called weekly by the investigator to check progress. Transcranial magnetic stimulation (TMS): For these tests, participants will sit in a chair that looks like one found at the dentist's office. A nerve stimulator will be placed on the wrist of the right hand to stimulate the median and ulnar nerves. The intensity of the nerve stimulator will be gradually increased until the right thumb begins to twitch. A magnetic coil will be placed on the scalp on the left side of the head, overlying the brain's motor cortex, to stimulate the brain's output to the muscles in the opposite hand. This procedure will be repeated using the left wrist and the right side of the head.
SF-36 Physical Functioning Subscore	68 units on a scale Standard Deviation 16	88 units on a scale Standard Deviation 18

PRIMARY outcome

Timeframe: absolute value at Week 12

Population: mean difference was calculated

This scale is an investigator-rated scale that measures illness severity on a single 7-point scale (1-7). Higher scores represent greater severity of illness.

Outcome measures

Measure	Botox Only n=8 Participants Participants randomized to receive Botox injections alone. Botox injection: Participants will receive a tailored dose of Botox to address their Cervical Dystonia symptoms Transcranial magnetic stimulation (TMS): For these tests, participants will sit in a chair that looks like one found at the dentist's office. A nerve stimulator will be placed on the wrist of the right hand to stimulate the median and ulnar nerves. The intensity of the nerve stimulator will be gradually increased until the right thumb begins to twitch. A magnetic coil will be placed on the scalp on the left side of the head, overlying the brain's motor cortex, to stimulate the brain's output to the muscles in the opposite hand. This procedure will be repeated using the left wrist and the right side of the head.	Botox Plus Physical Therapy n=8 Participants Participants randomized to receive Botox injection combined with Physical Therapy Botox injection: Participants will receive a tailored dose of Botox to address their Cervical Dystonia symptoms Physical Therapy: Participants will undergo physical therapy sessions with a physical therapist trained in movement disorders. Participants will be instructed to continue these exercises five times per week, and will be called weekly by the investigator to check progress. Transcranial magnetic stimulation (TMS): For these tests, participants will sit in a chair that looks like one found at the dentist's office. A nerve stimulator will be placed on the wrist of the right hand to stimulate the median and ulnar nerves. The intensity of the nerve stimulator will be gradually increased until the right thumb begins to twitch. A magnetic coil will be placed on the scalp on the left side of the head, overlying the brain's motor cortex, to stimulate the brain's output to the muscles in the opposite hand. This procedure will be repeated using the left wrist and the right side of the head.
Clinical Global Impression Scale (CGIS)	3 units on a scale Standard Deviation 1	2 units on a scale Standard Deviation 1

SECONDARY outcome

Timeframe: absolute value at week 12

Population: mean difference was calculated

A standard transcranial magnetic stimulation (TMS) paired associative stimulation (PAS) protocol was used to measure of neuroplasticity (the ability of the brain to form new connections). A nerve stimulator was placed on the wrist of the right hand to stimulate the median and ulnar nerves, set at the lowest intensity where the right thumb begins to twitch. An EMG sensor was placed over the abductor pollicis brevis muscle to measure muscle contractions. A magnetic coil was placed on the scalp on the left side of the head, overlying the brain's motor cortex, to stimulate the brain's output to the muscles in the opposite hand. 90 pairs of TMS and nerve stimulator pulses were applied. Then the motor evoked potential (MEP) from a single TMS pulse recorded from the surface EMG of the abductor pollicis brevis muscle was determined immediately, at 15 min and at 30 min after completion of the PAS protocol. The mean of these MEPs (PASmean) was compared between baseline and followup.

Outcome measures

Measure	Botox Only n=8 Participants Participants randomized to receive Botox injections alone. Botox injection: Participants will receive a tailored dose of Botox to address their Cervical Dystonia symptoms Transcranial magnetic stimulation (TMS): For these tests, participants will sit in a chair that looks like one found at the dentist's office. A nerve stimulator will be placed on the wrist of the right hand to stimulate the median and ulnar nerves. The intensity of the nerve stimulator will be gradually increased until the right thumb begins to twitch. A magnetic coil will be placed on the scalp on the left side of the head, overlying the brain's motor cortex, to stimulate the brain's output to the muscles in the opposite hand. This procedure will be repeated using the left wrist and the right side of the head.	Botox Plus Physical Therapy n=8 Participants Participants randomized to receive Botox injection combined with Physical Therapy Botox injection: Participants will receive a tailored dose of Botox to address their Cervical Dystonia symptoms Physical Therapy: Participants will undergo physical therapy sessions with a physical therapist trained in movement disorders. Participants will be instructed to continue these exercises five times per week, and will be called weekly by the investigator to check progress. Transcranial magnetic stimulation (TMS): For these tests, participants will sit in a chair that looks like one found at the dentist's office. A nerve stimulator will be placed on the wrist of the right hand to stimulate the median and ulnar nerves. The intensity of the nerve stimulator will be gradually increased until the right thumb begins to twitch. A magnetic coil will be placed on the scalp on the left side of the head, overlying the brain's motor cortex, to stimulate the brain's output to the muscles in the opposite hand. This procedure will be repeated using the left wrist and the right side of the head.
Mean MEP After Paired Associative Stimulation (PASmean)	1.7 millivolts Standard Deviation 0.5	1.3 millivolts Standard Deviation 0.6

OTHER_PRE_SPECIFIED outcome

Timeframe: absolute value at 12 weeks

Population: mean difference was calculated

This is a single item scale, on which participants will mark the level of pain from 0-10. Higher score represents more severe pain.

Outcome measures

Measure	Botox Only n=8 Participants Participants randomized to receive Botox injections alone. Botox injection: Participants will receive a tailored dose of Botox to address their Cervical Dystonia symptoms Transcranial magnetic stimulation (TMS): For these tests, participants will sit in a chair that looks like one found at the dentist's office. A nerve stimulator will be placed on the wrist of the right hand to stimulate the median and ulnar nerves. The intensity of the nerve stimulator will be gradually increased until the right thumb begins to twitch. A magnetic coil will be placed on the scalp on the left side of the head, overlying the brain's motor cortex, to stimulate the brain's output to the muscles in the opposite hand. This procedure will be repeated using the left wrist and the right side of the head.	Botox Plus Physical Therapy n=8 Participants Participants randomized to receive Botox injection combined with Physical Therapy Botox injection: Participants will receive a tailored dose of Botox to address their Cervical Dystonia symptoms Physical Therapy: Participants will undergo physical therapy sessions with a physical therapist trained in movement disorders. Participants will be instructed to continue these exercises five times per week, and will be called weekly by the investigator to check progress. Transcranial magnetic stimulation (TMS): For these tests, participants will sit in a chair that looks like one found at the dentist's office. A nerve stimulator will be placed on the wrist of the right hand to stimulate the median and ulnar nerves. The intensity of the nerve stimulator will be gradually increased until the right thumb begins to twitch. A magnetic coil will be placed on the scalp on the left side of the head, overlying the brain's motor cortex, to stimulate the brain's output to the muscles in the opposite hand. This procedure will be repeated using the left wrist and the right side of the head.
Visual Analog Scale	6 units on a scale Standard Deviation 3	4 units on a scale Standard Deviation 2

OTHER_PRE_SPECIFIED outcome

Timeframe: absolute value at 12 weeks was calculated

Population: mean difference was calculated

Participants will be asked to sit in a chair and move the head to the left, to the right, to the front, and to the back. Then, participants be asked to tilt the head from side to side. A goniometer will be used to measure how far the head is able to move. The goniometer is similar to a protractor that measures magnitude of angle. A greater number indicates a greater range of motion. The minimum score would be 0, with no definite maximum (would not clinically be expected to exceed 70 degrees).

Outcome measures

Measure	Botox Only n=8 Participants Participants randomized to receive Botox injections alone. Botox injection: Participants will receive a tailored dose of Botox to address their Cervical Dystonia symptoms Transcranial magnetic stimulation (TMS): For these tests, participants will sit in a chair that looks like one found at the dentist's office. A nerve stimulator will be placed on the wrist of the right hand to stimulate the median and ulnar nerves. The intensity of the nerve stimulator will be gradually increased until the right thumb begins to twitch. A magnetic coil will be placed on the scalp on the left side of the head, overlying the brain's motor cortex, to stimulate the brain's output to the muscles in the opposite hand. This procedure will be repeated using the left wrist and the right side of the head.	Botox Plus Physical Therapy n=8 Participants Participants randomized to receive Botox injection combined with Physical Therapy Botox injection: Participants will receive a tailored dose of Botox to address their Cervical Dystonia symptoms Physical Therapy: Participants will undergo physical therapy sessions with a physical therapist trained in movement disorders. Participants will be instructed to continue these exercises five times per week, and will be called weekly by the investigator to check progress. Transcranial magnetic stimulation (TMS): For these tests, participants will sit in a chair that looks like one found at the dentist's office. A nerve stimulator will be placed on the wrist of the right hand to stimulate the median and ulnar nerves. The intensity of the nerve stimulator will be gradually increased until the right thumb begins to twitch. A magnetic coil will be placed on the scalp on the left side of the head, overlying the brain's motor cortex, to stimulate the brain's output to the muscles in the opposite hand. This procedure will be repeated using the left wrist and the right side of the head.
Cervical Range of Motion Measurement	25 Angle in degrees Standard Deviation 14	26 Angle in degrees Standard Deviation 14

Adverse Events

Botox Only

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Botox Plus Physical Therapy

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Aparna Wagle Shukla

University of Florida

Phone: 3522945400

Email: aparna.shukla@neurology.ufl.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place