Transcutaneous Afferent Patterned Stimulation (TAPS) for Reduction of Parkinson's Disease (PD) Related Action Tremor

40 patients with PD with at least mild postural tremor were enrolled in a four-week, prospective, single-arm, open-label study of twice daily TAPS therapy. Due to the COVID-19 pandemic, TAPS devices were shipped to patients to run the study remotely. Unsupervised motion assessments were captured at home, and at the beginning and end of the four weeks by telemedicine.

• Cala Device (Device): transcutaneous afferent patterned stimulation (TAPS)

Primary outcomes

• Tremor Power [4 weeks]: Pre-specified effectiveness endpoints included improvements in (1) objective postural tremor power (primary outcome; assessed using an accelerometer on the device under standard of care medication state at home).

Secondary outcomes

• Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) [4 weeks]: Improvement of clinician-ratings of Movement Disorder Society Unified PD Rating Scale (MDS-UPDRS) Part III \[Goetz, C.G. et al. Wiley Intersci. 2008\] (co-secondary; in medication-off state). Clinician rated patients' tremor pre and post therapy on a scale of 0-4. 0=Normal (no tremor), 4=Severe.
• Bain and Findley Activities of Daily Living (BF-ADL) [4 weeks]: Improvement of patient-ratings of the Bain and Findley Activities of Daily Living (BF-ADL) \[Bain PG, et al. Journal of Neurol, Neuros \& Psych 1993\] (co-secondary; in medication-off state). Patients' rated ability to perform specific activities pre and post therapy on a scale from 1-4. 1=Able to do the activity without difficulty, 4=Cannot do the activity by yourself.
• Percentage of Patients With Clinician and Patient Global Impressions of Improvement Rated < 4 (CGI-I, PGI-I) [4 weeks]: Clinician and Patient global impressions of improvement (CGI-I, PGI-I; exploratory) post therapy. This is a rated scale from 1-7, with 1=Very Much Improved to 7=Very Much Worse. Percentage of patients with ratings < 4 (including very much improved, much improved and improved) were computed respectively for CGI-I and PGI-I.

Sex: All, ages: 22 Years to any

Inclusion Criteria:

* Must be ≥22 years of age
* Competent and willing to provide written, informed consent to participate in the study
* Clinically significant postural tremor as defined by:

  * Dominant hand/arm exhibiting postural tremor ≥ 2 (while in the off state) as assessed by the MDS-UPDRS postural tremor score
* Stable dose of Parkinson's disease medications, if applicable, for 30 days prior to study entry
* Willing to comply with study protocol requirements including:

  * Having the ability to do telemedicine or video calls for study visits
  * remaining on a stable dosage of Parkinson's medications, if applicable, during the duration of the study
  * no significant caffeine consumption within 8 hours of study visits

Exclusion Criteria:

* Implanted electrical medical device, such as a pacemaker, defibrillator, or deep brain stimulator
* 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 or dementia. These may include: multisystem atrophy, progressive supranuclear palsy, dementia with Lewy bodies, and Alzheimer's disease.
* 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
* Significant caffeine consumption within 8 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).
* 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

Participant flow

Outcome results

• Tremor Power (Primary), Median, Percentage of tremor power reduction: Single Arm - TAPS Delivered by Cala Device 64 (54 to 79)
• Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) (Secondary), Mean, units on a scale: Single Arm - TAPS Delivered by Cala Device 0.6 +/- 0.5
• Bain and Findley Activities of Daily Living (BF-ADL) (Secondary), Mean, units on a scale: Single Arm - TAPS Delivered by Cala Device 0.5 +/- 0.5
• Percentage of Patients With Clinician and Patient Global Impressions of Improvement Rated < 4 (CGI-I, PGI-I) (Secondary), Number, percentage of patients with improvement: Single Arm - TAPS Delivered by Cala Device 80

Adverse events

Time frame: 4 weeks

Other adverse events by term

• Study Protocol (PDF, 2020-10-01)
• Statistical Analysis Plan (PDF, 2021-03-25)