CalaTM
Health Care Professional FAQs
What is Cala TrioTM
Cala Trio therapy has three parts, the stimulator, the band, and the base station.
The device should NOT be used:
- by patients with an implanted electrical medical device, such as a pacemaker, defibrillator, or deep brain stimulator.
- by patients that have suspected or diagnosed epilepsy or other seizure disorder.
- by patients who are pregnant.
- on swollen, infected, inflamed areas, or skin eruptions, open wounds, or cancerous lesions.
Refer to the labeling for a complete list of contraindications, warnings and precautions.
Mechanism of Action
Cala Trio therapy delivers electrical stimulation to nerves in the wrist. These nerves project from the wrist to central brain networks that are responsible for generating hand tremor in essential tremor. Stimulation of the nerves in the wrist is thought to disrupt the network activity causing hand tremor and provide temporary and meaningful tremor reduction in your treated hand.
Cala Trio is a neuromodulation device that communicates with the body. Neuromodulation devices use electrodes to deliver stimulation to nerves in the body inhibiting signals or triggering neural impulses. Two aspects make Cala Trio unique, 1) delivering patterned peripheral nerve stimulation to the median and radial nerves that send signals to the brain, and 2) surface stimulation of the skin, avoiding surgical procedures.
With Cala Trio, therapy is calibrated to each patient’s specific tremor. The sensor in the device measures the frequency of tremor. Then during therapy, the device sends patterned stimulation to the median and radial nerves at the patient’s tremor frequency.
With Cala Trio, therapy is calibrated to the patient’s specific tremor motion by performing a tremor-inducing postural hold for 20 seconds. Tremor frequency is determined by measuring 3 postural holds, either Outstretched and Wing-beating postural holds, performed during setup. In order to calibrate therapy, prescribers should select the tremor-inducing task that exhibits the maximum tremor for each patient. The accelerometer in the device measures the patient’s tremor motion, calculates the dominant tremor frequency, and stores that information to deliver patterned stimulation to the median and radial nerves. During a stimulation session, the device sends this patterned stimulation to the median and radial nerves based on the patients’ tremor frequency. Tremor frequency in patients with essential tremor is typically 4-12 Hz.
The Cala Trio team initially explored stimulation of median, radial, and ulnar nerves. While the effect on the ulnar nerve is an area of research interest, early feedback from user testing suggested median and radial nerve stimulation were preferred.
Cala Trio stimulation is not expected to cause nerve or muscle fatigue. Stimulation-induced nerve block requires stimulation frequencies above 1,000 Hz [1], whereas the Cala Trio uses a frequency of 150 Hz. While neurotransmitter depletion at the synapse downstream of stimulation can occur at frequencies as low as 100 Hz [1], there were no instances of loss in sensory function observed with use of Cala Trio stimulation in the three-month PROSPECT study (n=263 patients). Long-term therapy habituation, which could be caused by synaptic changes at the brain level, was not observed over multiple months of use in the PROSPECT study
The stimulation amplitude is set below the threshold for motor nerve fiber recruitment, so stimulation-induced muscle fatigue is not expected during typical use of Cala Trio. The PROSPECT study showed that 0.4% of subjects had device-related weakness or lack of coordination in the treated hand.
Reference [1] Kilgore KL and Bhadra N, “Reversible nerve conduction block using kilohertz frequency alternating current,” Neuromodulation, 17(3): 242-55, 2014.
Clinical Evidence
In the PROSPECT study, a three-month, at-home clinical trial, clinicians (CGI-I) reported improvement in 68% of patients. This improvement is equivalent to a tremor reduction of 50%, comparable to first-line pharmacotherapies: propanolol and primidone, but without their side effect profile. Wrist-worn accelerometer recordings before and after 21,806 therapy sessions showed that 92% of patients improved, and 54% of patients experienced >=50% improvement in tremor power. <more>
In the PROSPECT study, a three-month, at-home clinical trial, 64% of patients reported persistent tremor relief after the 40 minutes of stimulation lasting on average 94 minutes (standard deviation = 138; median = 60). <more>
In our clinical study of Cala Trio therapy, participants who experienced tremor reduction from therapy observed this after the 40-minute stimulation session. We recommend using Cala Trio twice per day for two weeks to evaluate if and how therapy works for you. Note that the device is designed to provide at least five sessions when its battery is fully charged. With experience, users may find the frequency of use that works best for them.
The 40-minute stimulation duration was informed by research leading to the clinical study supporting Cala Trio labeling.
At present, it is not known if Cala Trio can/will reduce the need for medications. Cala Health continues to study Cala Trio therapy to better understand its use and efficacy in these situations.
Participants in clinical trials used this therapy as monotherapy or in combination with standard ET medications; in the PROSPECT study, a three-month, at-home clinical trial, 66% of patients were on ET medications. Medications included but were not limited to primidone, propranolol, and gabapentin. There were no reported interactions between Cala Trio therapy and medications prescribed to reduce ET symptoms. Cala Health continues to study Cala Trio therapy to better understand its use and efficacy in these situations. <more>
In clinical trials of Cala Trio, we did not specifically study medical refractory patients, or patients who show resistance to treatment. We studied two adjacently relevant characteristics.
- For patients on or off tremor medications, Cala therapy reduced tremor for both groups, and the improvements were not statistically different.
- Therapy reduced tremor whether patients reported previous ET treatment or not, and the improvements in these groups were not statistically different.
<more>
In the PROSPECT study on at-home use of Cala Trio therapy, 62% of patients with ‘severe’ or ‘moderate’ hand tremor improved to ‘mild’ or ‘slight’ as defined by TETRAS, a clinician-rated Tremor Research Group Essential Tremor Rating Assessment Scale. <more>
Additionally, real world evidence of therapy has shown that 93% of patients had a ≥2-fold improvement (i.e., 50% reduction) in tremor power during their most severe sessions (i.e., when tremor relief was most needed). <more>
Two single-session, randomized, controlled clinical trials have shown TAPS to improve tremor symptoms after a single session compared to a blinded sham (REF: Lin et al. 2018, Pahwa et al. 2019). A more recent three-month, single-arm, open-label at-home clinical trial showed these single-session therapeutic benefits are consistently reproduced over three months of repeated use (REF: Isaacson et al. 2020). The three-month trial was run without a blinded control arm due to the challenges of maintaining a patient blind for TAPS therapy over three months. Future research to establish robust methods to longitudinally maintain a patient blind for peripheral neuromodulation therapies would be a valuable asset for assessing novel therapies.
You can find a summary of references with PMID and DOI numbers for all the papers in Cala Trio Bibliography References. This list notes studies funded by Cala Health. It also includes studies cited in Cala Health’s white papers on Mechanism of Action and Safety.
Cala Trio Stimulation
Cala Trio delivers patterned stimulation to the median and radial nerves at the patient’s tremor frequency. The pulse pattern of this stimulation is provided continuously in bursts tuned around 4-12 Hz, the range of hand tremor due to essential tremor. The duration of each pulse is 300 usec to selectively activate peripheral Aβ sensory nerve fibers, and the frequency of this pulse is in the range of 50-150 Hz similar to deep brain stimulation used to treat essential tremor.
Cala Trio is a first-in-class therapy. It performs a significantly different function than TENS devices in relieving hand tremor compared to pain. It is also different in how it operates by delivering a stimulation therapy called transcutaneous afferent patterned stimulation (TAPS). Cala Trio combines these unique characteristics to provide a treatment individualized for a patient’s unique tremor.
Therapy with Cala Trio
The optimal stimulation level for Cala Trio therapy should be perceptible but comfortable tingling sensation in their thumb, pointer, middle, and ring fingers. Your patient may notice that as they move their hand around the intensity and location of sensation can change. Exactly where they position the device, the amount of water they apply to their wrist before putting the device on, and the stimulation level can affect the way they feel the stimulation sensation. The sensation should be strong, but they should be comfortable going about their daily life for the 40-minute stimulation session.
On the connector of each band, the size and handedness are marked, S, M, and L for small, medium and large and R and L for right and left.
Cala Trio band uses a proprietary skin interface, improving the experience of sticky hydrogel electrodes. The band can be used for months before needing to be replaced. The performance of the band deteriorates with exposure to dry skin, skins oils, and dust. Over the course of months, the band is eventually unable to support effective therapy. Cala Trio informs the user five days before a band needs to be replaced. Cala Health automatically supplies Cala Trio patients with one band every 3 months to maintain effective therapy.
Yes; the performance of the band deteriorates with exposure to dry skin, skin oils, and dust. Over the course of months, the band is eventually unable to support effective therapy. Cala Trio informs the user five days before a band needs to be replaced. Cala Health automatically supplies Cala Trio patients with one band every three months to maintain effective therapy.
It is recommended that other devices be used in separate sessions since no data has been published using electrical stimulation devices simultaneously with Cala Trio.
In 2021, Cala Trio will add a personalized digital experience to their therapy. It will help patients and their supporting clinicians learn about their use of Cala Trio therapy in managing their hand tremor. If you’re interested in learning about what Cala Trio can share with you about your tremor, click here to let us know.
Like a specialty pharmacy, Cala Trio Customer Success supports your patient throughout their use of therapy. When a prescription is recieved, Customer Success reaches out to them to discuss therapy, answer their questions including costs, and arrange shipment to them. Once delivered, they meet with your patient by phone or video to setup therapy; approximately 60% of the patients request this personal support. Additionally, there are instructions and videos to get started using Cala Trio. After this initial training, Customer Success continues to support them with Cala Trio including helping them understand how therapy best fits into their life.
When the battery is fully charged, it will last at least 5 sessions depending on your stimulation intensity. At a low battery level, it takes 3-4 hours to fully charge Cala Trio.
Cleaning Cala Trio band can help maintain a good connection between the band and your skin. To clean the band, use a disinfecting wipe on the inside of the band to wipe the three square, black electrodes. All other Cala Trio components can also be cleaned by using a disinfecting wipe as often as once per week.
Cala Trio therapy is designed for everyday use. The stimulator and base station have an expected service life of 3 years. The band has an expected service life of 90 days. To support everyday use, the stimulator has a 2-year warranty, and the band has a 45-day warranty.
Prescribing Cala Trio
Cala Trio therapy is indicated to treat essential tremor.
Cala Trio therapy is indicated for adults. The FDA defines adults as 22 years and older <more>
Cala Trio is FDA cleared to aid in the transient relief of hand tremors in the treated hand following stimulation in adults with essential tremor. All clinical measurements in Cala Trio clinical trials were specific to hand tremor only. No data was collected on head or neck tremor.
Cala Trio is indicated to treat essential tremor. The clinical studies published have included essential tremor patients. Further research is underway! Cala continues to learn and will share insights with the Neurology and Movement Disorder community as soon as we can.
Implanted electrical medical devices, such as a pacemaker, defibrillator, or DBS, are contraindicated because of the potential risk for interference with Cala Trio.
The contraindication comes from clinical studies of Cala Trio. This was a cautious indication taken due to the use of electrical current. Since seizures occur as a result of abnormal electrical activity in the brain, it was thought prudent to not use the therapy in patients with prior history of seizures. Through our experience thus far, we have not heard of the device causing seizure.
The device should NOT be used:
- by patients with an implanted electrical medical device, such as a pacemaker, defibrillator, or deep brain stimulator.
- by patients that have suspected or diagnosed epilepsy or other seizure disorder.
- by patients who are pregnant.
- on swollen, infected, inflamed areas, or skin eruptions, open wounds, or cancerous lesions.
Refer to the labeling for a complete list of contraindications, warnings and precautions.
Cala Trio therapy has not been studied on patients who are pregnant.
Patients using Cala Trio therapy have experienced two main side effects.
- Mild to moderate skin irritation, including sores, electrical stimulation burns or lesions, redness and/or itching at the site of stimulation: 11% in the PROSPECT trial
- Significant discomfort, electrical shock sensation, and pain: 4% in the PROSPECT trial
Of the 18% of patients who experienced a device-related adverse event, none of these were considered serious (see Table 4 in the PROSPECT publication).
For a full list of possible side effects, please see Adverse Reactions in the Health Care Professional Guide.
Consider the following for this patient:
- Stop therapy until healed
- Wash the affected area with soap and water
- Use hydrocortisone cream 2.5% or petroleum jelly to aid healing of the affected area
- Dress with gauze
- Do not use aloe vera
Once the affected area has healed, if you and the patient agree to continue using therapy, consider the following guidance:
- Reduce stimulation intensity to a level lower than used previously
- Add ample water over the entire wrist before each therapy session
- Tighten and position the band so that the electrodes are flush to the skin; this may include positioning the band higher or lower on the wrist so that the electrodes contact flatter or less curved areas of the wrist.
Download the prescription form online. Simple instructions are provided. Fax the prescription to 833-230-9251.
An electronic version can be downloaded and securely sent to CustomerSuccess@CalaTrio.com.
Fit and placement of the Cala Trio are essential to therapeutic efficacy. First, choose which hand to treat. Cala Trio is designed to stimulate nerves in the left OR right wrist; the uniquely-shaped stimulator connects to left and right bands differently. The device is NOT interchangeable between the left and right hand.
Next, measure the patient’s wrist circumference over the wrist bone (head of the ulna/styloid process) to determine band size. Read tips to measure wrist when the patient is self-measuring or if the measurement tool is not available, read tips here.
Like a specialty pharmacy, Cala Trio Customer Success manages this process. We guide your patient in setting up Cala Trio which includes
- Positioning and Fastening Cala Trio
- Calibrating Cala Trio
- Setting Therapy Intensity
See the section for Setting Up Cala Trio in the Health Care Professional Guide for details on each of these steps.
Like a specialty pharmacy, Cala Trio Customer Success supports your patient throughout their use of therapy. When a prescription is recieved, Customer Success reaches out to them to discuss therapy, answer their questions including costs, and arrange shipment to them. Once delivered, they meet with your patient by phone or video to setup therapy; approximately 60% of the patients request this personal support. Additionally, there are instructions and videos to get started using Cala Trio. After this initial training, Customer Success continues to support them with Cala Trio including helping them understand how therapy best fits into their life.
Because hand tremor varies day-to-day, it is difficult to evaluate the efficacy of Cala Trio therapy based on one session in clinic. This was seen in our clinical trials. Thus, we recommend using Cala Trio twice per day for two weeks to evaluate if and how therapy works for your patient. When you prescribe therapy for your patient, Cala Trio Customer Success will reach out to your patient by phone within 48 hours. We will work with your patient to arrange access and delivery of the therapy to start.
Clinicians and users do not need to adjust stimulation to optimize therapy. Cala Trio therapy is set up to be optimized to the frequency of your patient’s hand tremor. This frequency is automatically determined during setup in a series of Tremor Tasks a prescriber assigns a patient.
Clinicians and users can control two things, 1) comfort of the stimulation and 2) proper use of the therapy.
To control the comfort of stimulation, patients can adjust the intensity of Cala Trio therapy to a level that supports paresthesia and is comfortable while doing light activities. If it starts to feel uncomfortable when moving arm, wrist, hand, and fingers, they can decrease it.
To support the proper use of the therapy, a clinician can guide a patient in two ways. First, help confirm the patient feels paresthesia in some part of their hand, palm, and fingers from their middle finger to their thumb. Second, help guide the patient to adjust the stimulation intensity to a level that is comfortable for them while doing light activities like eating and drinking.
Yes, treatment for both hands is available with two (2) complete prescriptions.
Before prescribing two (2) Cala Trio devices, we recommend first prescribing one (1) Cala Trio device. After the patient confidently learns to manage the treatment of their hand tremor with Cala Trio, then consider prescribing the second one to treat the other hand.
Pricing and Reimbursement
As a novel, first-in class therapy, insurance coverage is not yet available. Insurance coverage for Cala Trio will take at least one year. We are working hard to keep that time frame as short as possible. We offer a number of payment options to accommodate patients’ financial situations. Cala Trio is a qualified medical expense for health savings accounts (HSA/FSA). Your patients can call us at (888) 699-1009 to learn about financing options and special pricing for qualified patients.