Essential Tremor
Conditions
Brief summary
Prospective, multi-center, randomized, controlled study designed to evaluate safety and repeatable effectiveness. Subjects will be randomized 2:1:1 to transcutaneous afferent patterned stimulation (TAPS), sham, or 'no intervention', respectively. Subjects randomized to the TAPS and sham arms will be blinded to their randomization assignments for the first two weeks of participation (controlled phase). After the first two weeks, all subjects will be crossed over to TAPS (open-label phase) for 2 weeks. During study participation, all subjects are to remain on a stable dosage of medications prescribed for the treatment of essential tremor, if applicable.
Interventions
DEVICECala ONE device
The Cala ONE device is a wrist-worn stimulator which applies a tremor-customized stimulation pattern to an individual's nerves.
Sponsors
Cala Health, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
The first two weeks of the study are double-blinded for the treatment and sham arms. The subjects and rating movement disorder neurologists will be blinded to the therapy allocation for the treatment and sham arms. The subjects in the 'no intervention' arm and their rating neurologists will not be blinded to their therapy allocation. The last two weeks are open-label, and all subjects will be given the option to use the Cala ONE device.
Intervention model description
The first two weeks are a 3-arm parallel design (treatment, sham, and 'no intervention'). The second two weeks are open-label (all subjects cross-over to treatment arm).
Eligibility
Sex/Gender
ALL
Age
22 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Must be ≥22 and ≤80 years of age * Competent and willing to provide written, informed consent to participate in the study * A diagnosis of essential tremor as confirmed from clinical history and examination by a movement disorder neurologist * Postural, action or intention tremor severity score of 2 or above in the dominant hand/arm as measured by the CRST rating scale * Significant disability due to essential tremor (Bain & Findley score of 3 or above in any one of the hand items) * Currently or previously prescribed either propranolol or primidone for the treatment of essential tremor * Stable dose of tremor medications for 30 days prior to study entry * Stable dose of antidepressant medications for 90 days prior to study entry * Willing to comply with study protocol requirements including: remaining on a stable dosage of tremor and antidepressant medications, if applicable, during the duration of the study; no significant alcohol or caffeine consumption within 12 hours of study visits; and no significant alcohol or caffeine consumption within 4 hours of twice-daily at home assessments during the controlled phase of the study
Exclusion criteria
* Moderate to severe ethanol dependence as defined by the criteria outlined in the DSM-5 (score of 4 or higher) * Implanted electrical medical device, such as a pacemaker, defibrillator, or deep brain stimulator * Previous thalamotomy procedure, including stereotactic thalamotomy, gamma knife radiosurgical thalamotomy, and focused ultrasound for the treatment of tremor * Suspected or diagnosed epilepsy or other seizure disorder * Swollen, infected, inflamed areas, or skin eruptions, open wounds, or cancerous lesions of skin at stimulation site * Peripheral neuropathy affecting the tested upper extremity * Presence of any other neurodegenerative disease like Parkinson-plus syndromes suspected on neurological examination. These include: multisystem atrophy, progressive supranuclear palsy, dementia with Lewy bodies, and Alzheimer's disease. * Anyone suspected to have the diagnosis of idiopathic Parkinson's disease (PD). This includes excluding anyone with the presence of parkinsonian features including bradykinesia rigidity, or postural instability. Subjects who exhibit only mild resting tremor but no other symptoms or signs of PD may be included. * Botulinum toxin injection for hand tremor within 6 months prior to study enrollment * Are participating or have participated in another interventional clinical trial in the last 30 days which may confound the results of this study, unless approved by the Sponsor * Are participating or have participated in another Cala Health clinical trial * Significant alcohol or caffeine consumption within 12 hours of study enrollment, which may confound the results of the study, where significant caffeine is considered more than 95 mg (equivalent to a cup of coffee), and significant alcohol is considered more than 14 g (equivalent to 5 oz of wine, 12 oz of beer, or 1.5 oz of distilled spirits). * Subjects unable to communicate with the investigator and staff * Any health condition that in the investigator's opinion should preclude participation in this study * Pregnancy or anticipated pregnancy during the course of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Tremor Power | Mean tremor power pre stimulation over two weeks of device usage as compared to mean tremor power post stimulation over two weeks of device usage. | For TAPS and sham arms, subjects will be prompted to perform a lateral postural hold prior to entering their PGI-S score before and after each stimulation session. During this hold, the device will record motion data to objectively assess if there are any changes in tremor level. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in Clinical Global Impression of Severity (CGI-S) | Collected before, during, and after in-office stimulation sessions at Week 0, Week 2, and Week 4 | Tremor severity will be assessed with the 7-point CGI-S scale at baseline for all arms. For TAPS and sham arms, CGI-S will also be assessed during and after stimulation. |
| Clinical Global Impression of Improvement (CGI-I) | Collected during and after in-office stimulation sessions at Week 0, Week 2, and Week 4 | For TAPS and sham arms, the blinded rating neurologist will assess improvements in tremor level during and after stimulation. |
| Change in Bain & Findley Activities of Daily Living (ADL) Scale | Collected before, during, and after in-office stimulation sessions at Week 0, Week 2, and Week 4. Collected via phone call Week 1 and Week 3. | The complete Bain & Findley ADL questionnaire will be administered at baseline for all arms. For TAPS and sham arms, a subset of ADLs relevant to upper limb tremor will be repeated with provided props during and after stimulation. On a weekly basis, all subjects will answer the complete Bain & Findley ADL questionnaire via phone call. |
| Subject Impression of Durability of Effect | Week 1, 2, 3 and 4. | TAPS and sham arms will also be asked how long their tremor relief lasts due to stimulation, if applicable. |
| Change in Quality of Life in Essential Tremor Questionnaire (QUEST) | Week 0, 2, and 4 | The QUEST assessment will be administered to all subjects during in-office visits (every 2 weeks). |
| Change in Clinical Rating Scale for Tremor (CRST) After Stimulation | Collected before and after in-office stimulation sessions at Week 2 | A complete CRST examination (also known as the Fahn-Tolosa-Marin Tremor Rating Scale) will be completed at baseline for all arms: TAPS, sham, and 'no intervention.' For TAPS and sham arms, a subset of CRST relevant to upper limb tremor will be repeated after stimulation. |
| Patient Global Impression of Improvement (PGI-I) | Collected during and after in-office stimulation sessions at Week 0, Week 2, and Week 4 | For TAPS and sham arms, the blinded subject will assess improvements in their tremor level during and after stimulation during office visits. |
| Subject Survey of Satisfaction | Week 4 | At the final visit, all subject will take a subject satisfaction survey which will include questions such as likelihood to recommend and other questions related to the usability of the device. |
| Device Usage Metrics | Week 4 | For TAPS and sham arms, the device will record usage metrics such as how many times the device was used per day and stimulation amplitude, to assess if there are any changes over time within group and within subject. |
| Change in Clinical Rating Scale for Tremor (CRST) During Stimulation | Collected before and during in-office stimulation sessions at Week 0, 2 and 4. | A complete CRST examination (also known as the Fahn-Tolosa-Marin Tremor Rating Scale) will be completed at baseline for all arms: TAPS, sham, and 'no intervention.' For TAPS and sham arms, a subset of CRST relevant to upper limb tremor will be repeated during stimulation. |
| Change in Patient Global Impression of Severity (PGI-S) | Before and after every stimulation session for TAPS and sham subjects through study completion. Twice daily for 'no intervention' subjects through study completion. | Tremor severity will be assessed with the 7-point PGI-S scale at baseline for all arms. For TAPS and sham arms, PGI-S will also be assessed during and after stimulation during office visits. Additionally, for TAPS and sham arms, PGI-S will be entered on the device before and after each stimulation session in the home environment. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| TAPS Subjects will receive a Cala ONE device that delivers TAPS, transcutaneous afferent patterned stimulation.
Cala ONE device: The Cala ONE device is a wrist-worn stimulator which applies a tremor-customized stimulation pattern to an individual's nerves. | 32 |
| Sham Subjects will receive a Cala ONE device that delivers sham stimulation.
Cala ONE device: The Cala ONE device is a wrist-worn stimulator which applies a tremor-customized stimulation pattern to an individual's nerves. | 15 |
| No Intervention Subjects will not receive a Cala ONE device, and will stay on their current treatment regimen for their essential tremor. | 15 |
| Total | 62 |
Baseline characteristics
| Characteristic | TAPS | Total | No Intervention | Sham |
|---|---|---|---|---|
| Age, Continuous | 67 years STANDARD_DEVIATION 8 | 67 years STANDARD_DEVIATION 9 | 67 years STANDARD_DEVIATION 9 | 66 years STANDARD_DEVIATION 11 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 31 Participants | 61 Participants | 15 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 30 Participants | 60 Participants | 15 Participants | 15 Participants |
| Region of Enrollment United States | 32 participants | 62 participants | 15 participants | 15 participants |
| Sex: Female, Male Female | 21 Participants | 34 Participants | 6 Participants | 7 Participants |
| Sex: Female, Male Male | 11 Participants | 28 Participants | 9 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 32 | 0 / 15 | 0 / 15 |
| other Total, other adverse events | 5 / 32 | 1 / 15 | 1 / 15 |
| serious Total, serious adverse events | 0 / 32 | 0 / 15 | 0 / 15 |
Outcome results
Primary
Percent Change in Tremor Power
For TAPS and sham arms, subjects will be prompted to perform a lateral postural hold prior to entering their PGI-S score before and after each stimulation session. During this hold, the device will record motion data to objectively assess if there are any changes in tremor level.
Time frame: Mean tremor power pre stimulation over two weeks of device usage as compared to mean tremor power post stimulation over two weeks of device usage.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| TAPS | Percent Change in Tremor Power | 43 percent tremor improvement | Standard Deviation 4 |
| Sham | Percent Change in Tremor Power | 9 percent tremor improvement | Standard Deviation 10 |
Other Pre-specified
Change in Bain & Findley Activities of Daily Living (ADL) Scale
The complete Bain & Findley ADL questionnaire will be administered at baseline for all arms. For TAPS and sham arms, a subset of ADLs relevant to upper limb tremor will be repeated with provided props during and after stimulation. On a weekly basis, all subjects will answer the complete Bain & Findley ADL questionnaire via phone call.
Time frame: Collected before, during, and after in-office stimulation sessions at Week 0, Week 2, and Week 4. Collected via phone call Week 1 and Week 3.
Other Pre-specified
Change in Clinical Global Impression of Severity (CGI-S)
Tremor severity will be assessed with the 7-point CGI-S scale at baseline for all arms. For TAPS and sham arms, CGI-S will also be assessed during and after stimulation.
Time frame: Collected before, during, and after in-office stimulation sessions at Week 0, Week 2, and Week 4
Other Pre-specified
Change in Clinical Rating Scale for Tremor (CRST) After Stimulation
A complete CRST examination (also known as the Fahn-Tolosa-Marin Tremor Rating Scale) will be completed at baseline for all arms: TAPS, sham, and 'no intervention.' For TAPS and sham arms, a subset of CRST relevant to upper limb tremor will be repeated after stimulation.
Time frame: Collected before and after in-office stimulation sessions at Week 0 and 4.
Other Pre-specified
Change in Clinical Rating Scale for Tremor (CRST) After Stimulation
A complete CRST examination (also known as the Fahn-Tolosa-Marin Tremor Rating Scale) will be completed at baseline for all arms: TAPS, sham, and 'no intervention.' For TAPS and sham arms, a subset of CRST relevant to upper limb tremor will be repeated after stimulation.
Time frame: Collected before and after in-office stimulation sessions at Week 2
Other Pre-specified
Change in Clinical Rating Scale for Tremor (CRST) During Stimulation
A complete CRST examination (also known as the Fahn-Tolosa-Marin Tremor Rating Scale) will be completed at baseline for all arms: TAPS, sham, and 'no intervention.' For TAPS and sham arms, a subset of CRST relevant to upper limb tremor will be repeated during stimulation.
Time frame: Collected before and during in-office stimulation sessions at Week 0, 2 and 4.
Other Pre-specified
Change in Patient Global Impression of Severity (PGI-S)
Tremor severity will be assessed with the 7-point PGI-S scale at baseline for all arms. For TAPS and sham arms, PGI-S will also be assessed during and after stimulation during office visits. Additionally, for TAPS and sham arms, PGI-S will be entered on the device before and after each stimulation session in the home environment.
Time frame: Before and after every stimulation session for TAPS and sham subjects through study completion. Twice daily for 'no intervention' subjects through study completion.
Other Pre-specified
Change in Quality of Life in Essential Tremor Questionnaire (QUEST)
The QUEST assessment will be administered to all subjects during in-office visits (every 2 weeks).
Time frame: Week 0, 2, and 4
Other Pre-specified
Clinical Global Impression of Improvement (CGI-I)
For TAPS and sham arms, the blinded rating neurologist will assess improvements in tremor level during and after stimulation.
Time frame: Collected during and after in-office stimulation sessions at Week 0, Week 2, and Week 4
Other Pre-specified
Device Usage Metrics
For TAPS and sham arms, the device will record usage metrics such as how many times the device was used per day and stimulation amplitude, to assess if there are any changes over time within group and within subject.
Time frame: Week 4
Other Pre-specified
Patient Global Impression of Improvement (PGI-I)
For TAPS and sham arms, the blinded subject will assess improvements in their tremor level during and after stimulation during office visits.
Time frame: Collected during and after in-office stimulation sessions at Week 0, Week 2, and Week 4
Other Pre-specified
Subject Impression of Durability of Effect
TAPS and sham arms will also be asked how long their tremor relief lasts due to stimulation, if applicable.
Time frame: Week 1, 2, 3 and 4.
Other Pre-specified
Subject Survey of Satisfaction
At the final visit, all subject will take a subject satisfaction survey which will include questions such as likelihood to recommend and other questions related to the usability of the device.
Time frame: Week 4