(263 days)
Not Found
Not Found
No
The summary describes a non-invasive electrical stimulation device and does not mention any AI or ML components or capabilities.
Yes
The device is used to therapeutically stimulate the Trigeminal nerve for the treatment of pediatric Attention Deficit Hyperactivity Disorder, indicating a therapeutic purpose.
No
The device is indicated for "treatment of pediatric Attention Deficit Hyperactivity Disorder," not diagnosis. It uses electrical stimulation as a therapy.
No
The device description explicitly states it has two primary hardware components: an external pulse generator and electrical patches.
Based on the provided information, this device is not an IVD (In Vitro Diagnostic).
Here's why:
- IVD Definition: In Vitro Diagnostics are medical devices used to examine specimens taken from the human body (like blood, urine, tissue) to provide information for diagnosis, monitoring, or screening.
- Device Function: The Monarch external Trigeminal Nerve Stimulation (eTNS) System is a therapeutic device that uses electrical stimulation applied externally to the forehead to treat ADHD. It does not analyze any biological samples from the patient.
- Intended Use: The intended use is for treatment of ADHD, not for diagnosis or analysis of biological specimens.
Therefore, the Monarch eTNS System falls under the category of a therapeutic medical device, not an In Vitro Diagnostic.
N/A
Intended Use / Indications for Use
The Monarch external Trigeminal Nerve Stimulation (eTNS) System is indicated for treatment of pediatric Attention Deficit Hyperactivity Disorder as a monotherapy in patients ages 7 through 12 years old who are not currently taking prescription ADHD medications. The device is used for patient treatment by prescription only and is intended to be used in the home under the supervision of a caregiver during periods of sleep.
Product codes
OGL, QGL
Device Description
The Monarch external Trigeminal Nerve Stimulation (eTNS) System is a non-invasive device that uses electrical signals to therapeutically stimulate the Trigeminal nerve. The primary components of the device are:
- The Monarch external pulse generator
- The Monarch NS-2 external (cutaneous) electrical patches, which are single use ● disposable patches worn on the forehead.
The device has two primary components A) an external pulse generator approximately the size of a cell phone, and B) the non-invasive electrical patch that patients apply to their forehead to receive therapy.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Supraorbital (SO) and Supratrochlear (ST) nerves of the V1 division of the Trigeminal Nerve (Forehead)
Indicated Patient Age Range
7 through 12 years old
Intended User / Care Setting
Prescription only and is intended to be used in the home under the supervision of a caregiver during periods of sleep.
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies
Two clinical trials, eTNS-ADHD01 (Study 1) and eTNS-ADHD02 (Study 2), were conducted.
Study 1 - eTNS-ADHD01 (NCT01388530)
- Study type: Open label trial
- Sample size: 24 children ages 7 through 14 with moderate to severe ADHD. 25 met inclusion/exclusion criteria, 24 initiated eTNS treatment. 22 participants with baseline and visit 4 data for treatment analysis.
- Key results:
- Safety: 13 adverse events reported. 2 events (eye twitching and headache) were deemed potentially related.
- Effectiveness: Mean ADHD-RS score decreased from 32.6 at baseline to 18.2 at week 4 and 17.3 at week 8.
- Limitations: Small sample size, open label studies may overestimate treatment effect, do not assess placebo response or the effect of other treatments.
Study 2 - eTNS-ADHD02 (NCT02155608)
- Study type: Double blind, randomized, sham controlled trial.
- Sample size: 62 subjects enrolled and randomized (32 to active, 30 to sham). 59 subjects completed the 4-week double blind treatment period (31 in active, 28 in sham).
- Key results:
- Blinding Assessment: No significant difference in caregiver expectations between active and sham groups regarding expectations of a positive treatment effect (P Value .50 for success, .37 for help).
- Primary Efficacy Endpoint (ADHD-IV Rating Scale): Average ADHD-RS score in the active group decreased from 34.1 points at baseline to 23.4 points. In the sham group, a decrease from 33.7 points at baseline to 27.5 points was recorded. Both groups showed decrease over Week 1, followed by ongoing improvement in the active group and flattening in the sham group. Treatment effect size demonstrated a medium effect in ADHD-RS Total scores using Cohen's d test.
- Secondary Efficacy Endpoint (CGI-I): After 4 weeks, 52% of subjects in the active group improved by one or more points on the CGI-I scale versus 14% of subjects in the sham group (P Value 0.003). Steadily increasing improvement in active group vs. no significant change in sham group.
- Safety: No significant differences in vital signs between baseline and week 4 or between active and sham treatment groups. eTNS was well tolerated; all adverse events were mild to moderate in severity. No serious adverse events (SAEs).
- Limitations: Small sample size, potential for unblinding subjects in the sham arm resulting in patient bias, design did not allow assessment of placebo response.
Long Term Data
- Subset of patients from Study 2 (those with CGI-I score of
§ 882.5898 Transcutaneous electrical nerve stimulator for attention deficit hyperactivity disorder.
(a)
Identification. A transcutaneous electrical nerve stimulator for attention deficit hyperactivity disorder (ADHD) is a prescription device that stimulates transcutaneously or percutaneously through electrodes placed on the forehead.(b)
Classification. Class II (special controls). The special controls for this device are:(1) The patient-contacting components of the device must be demonstrated to be biocompatible.
(2) Performance testing must demonstrate the electromagnetic compatibility and electrical, mechanical, and thermal safety of the device.
(3) Non-clinical performance testing must demonstrate that the device performs as intended under anticipated conditions of use. The following must be performed:
(i) Electrical performance testing must validate electrical output and duration of stimulation;
(ii) Battery performance testing must be performed; and
(iii) Adhesive integrity testing of the electrodes must be conducted.
(4) The technical parameters of the device including waveform, maximum output current and voltage, pulse duration, frequency, net charge per pulse, maximum current density, maximum average current, and maximum average power density must be fully characterized.
(5) Software verification, validation, and hazard analysis must be performed.
(6) Shelf life testing of the electrodes must be performed to demonstrate continued package integrity and component functionality over the labeled shelf life.
(7) Labeling must include the following:
(i) A contraindication for patients with an implanted metallic or electronic device in the head, a cardiac pacemaker, or an implanted or wearable defibrillator;
(ii) A warning that the device is only for use on clean, intact skin;
(iii) Information on how the device operates and the typical sensations experienced during treatment;
(iv) A detailed summary of the device technical parameters;
(v) A shelf life for the electrodes;
(vi) Instructions for use, including placement of the device on the patient; and
(vii) Cleaning instructions.
0
DE NOVO CLASSIFICATION REQUEST FOR MONARCH ETNS SYSTEM
REGULATORY INFORMATION
FDA identifies this generic type of device as:
Transcutaneous electrical nerve stimulator for Attention Deficit Hyperactivity Disorder. A transcutaneous electrical nerve stimulator for Attention Deficit Hyperactivity Disorder (ADHD) is a prescription device that stimulates transcutaneously or percutaneously through electrodes placed on the forehead.
NEW REGULATION NUMBER: 21 CFR 882.5898
CLASSIFICATION: Class II
PRODUCT CODE: OGL
BACKGROUND
DEVICE NAME: Monarch eTNS System
SUBMISSION NUMBER: DEN180041
DATE OF DE NOVO: July 31, 2018
NeuroSigma, Inc. CONTACT: 10960 Wilshire Boulevard Suite 1910 Los Angeles. CA 90024
INDICATIONS FOR USE
The Monarch external Trigeminal Nerve Stimulation (eTNS) System is indicated for treatment of pediatric Attention Deficit Hyperactivity Disorder as a monotherapy in patients ages 7 through 12 years old who are not currently taking prescription ADHD medications. The device is used for patient treatment by prescription only and is intended to be used in the home under the supervision of a caregiver during periods of sleep.
LIMITATIONS
For prescription use only.
The device is contraindicated for use by patients with:
- Implanted cardiac and/or neurostimulation systems ●
- Implanted metallic or electronic device in their head 0
1
The device should not be applied on the neck or chest, and it should not be used in the presence of electric monitoring equipment (e.g. cardiac monitors), in the bath or shower, or while operating machinery.
The long-term effects of using the Monarch eTNS System are unknown.
The device should only be applied to healthy, clean, intact skin.
PLEASE REFER TO THE LABELING FOR A MORE COMPLETE LIST OF WARNINGS, PRECAUTIONS AND CONTRAINDICATIONS.
DEVICE DESCRIPTION
The Monarch external Trigeminal Nerve Stimulation (eTNS) System is a non-invasive device that uses electrical signals to therapeutically stimulate the Trigeminal nerve. The primary components of the device are:
- The Monarch external pulse generator
- The Monarch NS-2 external (cutaneous) electrical patches, which are single use ● disposable patches worn on the forehead.
| NeuroSigma |
|---|
| Mirach |
| A) Pulse generator, electrode patch on forehead, and system as worn | B) Illustration of NS-2 Electrical Patch placed on forehead |
|---|---|
| --------------------------------------------------------------------- | ------------------------------------------------------------- |
The device has two primary components A) an external pulse generator approximately the size of a cell phone, and B) the non-invasive electrical patch that patients apply to their forehead to receive therapy.
Figure 1: Monarch eTNS System
The Monarch External Pulse Generator
The Monarch pulse generator generates an electrical stimulus for delivery to the patient's forehead. It is housed in a sealed protective case and powered by a rechargeable lithium polymer battery. Accessories include two spare batteries and a battery charging station. The stimulation parameters generated by the Monarch eTNS System are summarized in Table 1. All parameters are fixed except for amplitude is controlled by the patient's caregiver. Under a
2
physician's supervision, the user can adjust the amplitude in 0.2mA increments, from 0 and 10 mA.
The Monarch NS-2 Electrical Patch
The Monarch eTNS patch attaches to the skin of the forehead by both hypoallergenic hydrogel and medical grade foam and adhesive and allows for bilateral stimulation of both the right and left supraorbital (SO) and supratrochlear (ST) branches of the trigeminal nerve (V1), located above the eyebrows in the forehead. The caretaker places the patch in the midline of the patient's forehead and applies the patch to the forehead directly above the eyebrows.
The gel, foam, and adhesive have undergone skin sensitization and histocompatibility studies in animals according to ISO 10993-1: Biological Evaluation of Medical Devices – Part 1: Evaluation and Testing. The electrical patch is connected to the pulse generator via a lead wire.
Stimulation Parameters:
Electrical Stimulation parameters generated by the Monarch eTNS System are summarized in the table below:
3
| Parameter | Outcome |
|---|---|
| Waveform | Symmetrical Square Wave |
| Frequency of Stimulation | 120 Hz |
| Pulse Width | 250 $\mu$ Sec |
| Duration between pulses | 8 mSec |
| Maximum stimulus intensity | 10 mA, under patient control |
| Maximum Output Voltage | 5.36V |
| Hours of use | 7 – 9 hours, while asleep, as prescribed by treating physician |
| Cycling | 30 Sec ON: 1 Sec Ramp Down: 30 Sec OFF: 1 Sec Ramp Up |
| Net Charge per pulse | |
| Maximum current density | 1.4 mA.cm2 |
| Maximum average power density | 7.5 mW/cm2 |
| Maximum average current | 10 mA |
| Maximum Charge Density | 0.35 $\mu$ C/cm2 |
| Maximum Average power density | 7.5 mW/cm2 |
| Stimulating Surface Area of NS-2 Patch | 7.1 cm2 per electrode |
| Anatomical Target | Supraorbital (SO) and Supratrochlear (ST) nerves of |
| the V1 division of the Trigeminal Nerve |
Table 1: Stimulation Parameters
4
Principle of Operation:
The Monarch eTNS System treatment protocol is administered each night while the patient is sleeping, for 7 - 9 hours. The device is designed to provide non-invasive electrical stimulation of the trigeminal nerve. The trigeminal nerve is the largest cranial nerve and has three major sensory divisions of the face (V1, V2, V3), all of which are bilateral. The trigeminal nerve provides a direct connection to multiple brain structures implicated in ADHD and other neurologic and neuopsychiatric disorders. 1234
Image /page/4/Figure/2 description: The image contains three diagrams labeled A, B, and C. Diagram A shows the trigeminal nerve and its three branches: V1 (ophthalmic zone), V2 (maxillary zone), and V3 (mandibular zone). Diagram B shows the supraorbital and supratrochelar nerves on a skull. Diagram C shows the cortex and thalamus.
A) The Trigeminal nerve provides sensation to the face via three divisions (V1, V2, V3). eTNS stimulates the V1 division. B) The Supraorbital (SO) and Supratrochlear (ST) nerves are terminal branches of the V1 division. These four nerves, two on each side of the forehead, are the stimulation targets for eTNS. C) Path of the Trigeminal as it enters the brainstem at the Pons then makes connections in the medulla and midbrain before making connections in the thalamus and cortex. Figure 2: Anatomy of the Trigeminal Nerve
SUMMARY OF NONCLINICAL AND BENCH STUDIES
Biocompatibility, electrical safety, electromagnetic compatibility, battery safety, waveform verification. shelf life and software testing was required for the Monarch eTNS System.
BIOCOMPATIBILITY/MATERIALS
Patient contacting materials of the Monarch eTNS System are limited to the materials of the NS-2 electrode patch
| Patient Contacting
Device Component | Nature of Tissue
Contact | Duration of Tissue Contact |
|-------------------------------------------------------------------|-------------------------------------|-----------------------------------|
| NS-2 Electrical Patch /
Hydrogel (Multistick
MG-1500 AG600) | Skin Contact | 7 – 9 hours; During Sleep |
1 Nolte J. The Human Brain. An introduction to its functional anatomy. Mosby. 6thedition. 2009.
2 Caous CA, de Sousa Buck H, Lindsey CJ. Neuronal connections of the paratrigeminal nucleus. AutonNeurosci 2001; 94:14-24.
3 Grzanna R, Chee WK, Akeyson EW. Noradrenergic projections to brainstem nuclei: evidence for differential projections from noradrenergic subgroups. J Comp Neurol 1987; 263:76-91.
4 Krout KE, Belzer RE, Loewy AD. Brainstem projections to midline and intra-laminar thalamic nuclei of the rat. J Comp Neurol 2002; 448:53-101.
5
| NS-2 Electrical Patch /
adhesive foam
| (MTDID 22459 A3) | Skin Contact | 7 – 9 hours; During Sleep |
|---|---|---|
| -------------------------------------------------------------- | -------------- | --------------------------- |
Table 2: List of Patient-Contacting Materials
The electrode has limited duration (2.
Table 13: CGI-I by Study Week
d) Study 2 Limitations
Additional factors to be considered in determining a reasonable assurance of safety and effectiveness includes the small sample size and the potential for unblinding subjects in the sham arm which may have resulted in patient bias and the outcomes reported for treatment groups. In addition, the design of Study 2 did not allow an assessment of the placebo response.
LABELING
The Monarch eTNS System Instructions for Use are consistent with the clinical data and cover all the hazards and other clinically relevant information that may impact use of the device. The labeling is sufficient and satisfies the requirements of 21 CFR § 801.109 Prescription devices. The Monarch eTNS System is contraindicated for the following uses:
The device is contraindicated for use by patients with:
- Implanted cardiac and/or neurostimulation systems ●
- . Implanted metallic or electronic device in their head
The following warnings and precautions are included within device labeling:
- The device should not be applied on the neck or chest, and it should not be used in the 0 presence of electric monitoring equipment (e.g. cardiac monitors), in the bath or shower, or while operating machinery.
- The long-term effects of using the Monarch eTNS System are unknown. ●
- The device should be used only as direct and be applied to healthy, clean, intact skin. o
The labeling also includes:
- Information on how the device operates and the typical sensations experienced during treatment;
- A detailed summary of the device technical parameters; ●
- A shelf life for the electrodes; ●
- Information in the Instructions for Use regarding how to place the device on the patient; and
- Cleaning instructions for the device.
RISKS TO HEALTH
20
The table below identifies the risks to health that may be associated with use of a transcutaneous nerve stimulator for Attention Deficit Hyperactivity Disorder (ADHD) and the measures necessary to mitigate these risks.
| Identified Risk | Mitigation Measures |
|---|---|
| Adverse tissue reaction | Biocompatibility evaluation |
| Injury or discomfort from | |
| electrical stimulation, including | |
| burns and nerve damage | Electromagnetic compatibility testing |
| Electrical, mechanical, and thermal safety testing | |
| Non-clinical performance testing | |
| Software verification, validation, and hazard analysis | |
| Shelf life testing | |
| Labeling | |
| Misuse that may result in device | |
| failure, user discomfort, or | |
| injury | Labeling |
| Skin irritation or infection from | |
| use on broken skin | Labeling |
Table 14: Identified Risks to Health and Mitigation Measures
SPECIAL CONTROLS:
In combination with the general controls of the FD&C Act, the transcutaneous electrical nerve stimulator for Attention Deficit Hyperactivity Disorder (ADHD) is subject to the following special controls:
-
- The patient-contacting components of the device must be demonstrated to be biocompatible.
-
- Performance testing must demonstrate the electromagnetic compatibility and electrical, mechanical, and thermal safety of the device.
-
- Non-clinical performance testing must demonstrate that the device performs as intended under anticipated conditions of use. The following must be performed:
- a. Electrical performance testing must validate electrical output and duration of stimulation;
- b. Battery performance testing must be performed; and
- c. Adhesive integrity testing of the electrodes must be conducted.
-
- The technical parameters of the device including waveform, maximum output current and voltage, pulse duration, frequency, net charge per pulse, maximum current density, maximum average current, and maximum average power density must be fully characterized.
-
- Software verification, validation, and hazard analysis must be performed.
21
-
- Shelf life testing of the electrodes must be performed to demonstrate continued package integrity and component functionality over the labeled shelf life.
-
- Labeling must include the following:
- a. A contraindication for patients with an implanted metallic or electronic device in the head, a cardiac pacemaker, or an implanted or wearable defibrillator;
- b. A warning that the device is only for use on clean, intact skin;
- c. Information on how the device operates and the typical sensations experienced during treatment;
- d. A detailed summary of the device technical parameters;
- A shelf life for the electrodes; e.
- Instructions for use, including placement of the device on the patient; and f.
- g. Cleaning instructions.
BENEFIT/RISK DETERMINATION
The risks of the Monarch eTNS Therapy System are based on data collected from two studies. No serious adverse events were reported in either study and all adverse events were minor with reversible effects. In Study 2, differences in side effects seen between patients in the active compared to the sham group included nightmares, headache, frequent urination, increased appetite, skin rash, and teeth clenching. However, none of the patients were reported to discontinue treatment based on headaches or any of the other adverse effects.
The probable benefits of the device are based on data collected from the randomized shamcontrolled trial that demonstrated a clinically meaningful and statistically significant improvement in the ADHD-RS total score over the 4-week treatment period. Data from both Study 1 and long term follow up portion of Study 2 indicates that there may be continued benefit beyond 4 weeks. However, this benefit was not studied in a controlled manner.
Additional factors considered in determining probable risks and benefits for the Monarch eTNS Therapy System include:
-
- Medications approved for ADHD provide a similar benefit but may have problematic side effects.
-
- Long term effects of eTNS therapy (beyond 4 weeks) has not been evaluated.
-
- Blinding was not assessed after the week 1 assessment in the one blinded trial.
Based on the results of the feasibility study and the randomized, sham controlled, clinical trial to support the use of a transcutaneous nerve stimulator for the treatment of ADHD in a pediatric population (ages 7 - 12, and assessment of the adverse event reported, we conclude that the benefits outweigh the probable risks.
Patient Perspectives
Patient and caregiver self-reported measures along with patient diaries were used to collect information on patient perspectives for this device.
22
Benefit/Risk Conclusion
In conclusion, given the available information above, the data support that for the previously stated indications for use, the probable benefits outweigh the probable risks for the Monarch eTNS System. The device provides benefits and the risks can be mitigated using general controls and the identified special controls.
CONCLUSION
The De Novo request for the Monarch eTNS Therapy System is granted and the device is classified under the following:
Product Code: QGL Device Type: Transcutaneous electrical nerve stimulator for Attention Deficit Hyperactive Disorder Class: II Regulation: 21 CFR 882.5898
REFERENCES
-
- Nolte J. The Human Brain. An introduction to its functional anatomy. Mosby. 6th edition. 2009.
-
- Caous CA, de Sousa Buck H, Lindsey CJ. Neuronal connections of the paratrigeminal nucleus. AutonNeurosci 2001; 94:14-24.
-
- Grzanna R, Chee WK, Akeyson EW. Noradrenergic projections to brainstem nuclei: evidence for differential projections from noradrenergic subgroups. J Comp Neurol 1987; 263:76-91.
-
- Krout KE, Belzer RE, Loewy AD. Brainstem projections to midline and intra-laminar thalamic nuclei of the rat. J Comp Neurol 2002; 448:53-101.
-
- McGough et al. An Eight-week. Open-trial. Pilot Feasibility Study of Trigeminal Nerve Stimulation in Youth With Attention-deficit/Hyperactivity Disorder. Brain Stimulation 8 (2015) 299-304.
-
- McGough JJ, Sturm A, Cowen J, Tung K, Salgari GC, Leuchter AF, Cook IA, Sugar CA, Loo SK. Double-Blind, Sham-Controlled, Pilot Study of Trigeminal Nerve Stimulation for Attention-Deficit/Hyperactivity Disorder. J Am Acad Child Adolesc Psychiatry. 2019 Apr;58(4):403-411.e3. doi: 10.1016/j.jaac.2018.11.013. Epub 2019 Jan 28.