Official Translation from Romanian Into English

Official Translation from Romanian Into English

OFFICIAL TRANSLATION FROM ROMANIAN INTO ENGLISH

BIOFEEDBACK 2014 SRL

Bdul. Henri Coandă, nr.2, Cam. 14, Satu Mare, Romania

Tel./Fax: 0261.716.405

Web: E-mail:

Clinical Investigation Report

Clinical Investigation Report

Clinical Investigation Report

TITLE OF THE CLINICAL INVESTIGATION:

'USE OF THE ELECTROPHYSIOLOGICAL BIOFEEDBACK SYSTEM

EDUCTOR Biofeedback System IN

  • STRESS DETECTION AND REDUCTION
  • MUSCULAR REEDUCATION
  • PAIN TREATMENT
  • PREGNANCY STABILITY IMBALANCE (DETECTION OF MEDICAL CONDITIONS)'

CODE OF THE CLINICAL INVESTIGATION:

BFK-01

Monocentric and comparative clinical investigation

Clinical Investigation Plan

BFK-CIP-01

Clinical investigation carried out in accordance with the standard

SR EN ISO 14155:2012

Date: October 20TH, 2015

Author: Dr. Dima Augustin

Primary Care Physician in Physical Recovery and Balneophysiotherapy

[signature and stamp]

Table of contents

1 SUMMARY ...... 4

1.1 Title of the clinical investigation...... 4

1.2 Introduction...... 4

1.3 Demographic data of the patients...... 4

1.4 Results...... 5

1.5 Conclusions...... 6

2 INTRODUCTION...... 7

3 Biofeedback System EDUCTOR DEVICE AND METHODS...... 8

3.1 Description of the Universal Electrophysiological Biofeedback System EDUCTOR...... 8

3.2 Clinical Investigation Plan...... 8

3.2.1 Subjects of the clinical investigation...... 9

3.2.2 Procedures carried out by subjects during the clinical investigation...... 10

3.2.3 Treatment / concomitant medication...... 11

3.2.4. Duration of the subjects' evaluation...... 12

3.2.5. Statistical analysis...... 12

4 RESULTS...... 21

4.1 Arrangement of the subjects and the devices EDUCTOR Biofeedback System...... 21

4.1.1 Demographic data of the subjects...... 21

4.1.2 Medical history of the subjects...... 21

4.1.3 Blood group...... 22

4.1.4 Compliance with the Clinical Investigation Plan, BFK-CIP-01...... 22

4.2 Analysis of the performances provided in the Clinical Investigation Plan, BFK-CIP-01....22

4.2.1 Data about depression, anxiety and stress, muscular reeducation, pain treatment and detection of the medical conditions 22

4.2.2 Depression, anxiety and stress of the subjects...... 24

4.2.3 Muscular dystonia...... 26

4.2.4 Muscle contracture...... 28

4.2.5 Intensity of the pain felt by the subjects...... 28

4.2.6 Detection of the medical conditions of the patients...... 36

4.2.7 Subjects' perception on the extent to which the daily activities and the leisure time activities were restricted 38

4.2.8 The success of the treatment appreciated by patients...... 42

4.2.9 Tolerance and acceptability of the Universal Electrophysiological Biofeedback System EDUCTOR 45

4.3 Summary of the adverse events and the adverse effects...... 46

4.4 Deficiencies of the Universal Electrophysiological Biofeedback System EDUCTOR...... 46

4.5 Manner of treating the lost data, irregularities, including regarding the subjects...... 46

5 DISCUSSION AND CONCLUSIONS...... 47

5.1 Results in terms of safety and performance...... 47

5.2 Assessment of risks and benefits...... 48

5.3 Clinical relevance of data and results...... 48

5.4 Benefits specific to or precautions necessary to the patients or some subgroups...... 51

5.5 Implications on the future clinical investigations...... 51

5.6 Limitations of the clinical investigation...... 51

6 ABBREVIATIONS; TERMS AND DEFINITIONS...... 53

7 ETHICS...... 54

8 INVESTIGATORS AND ADMINISTRATIVE STRUCTURE OF THE CLINICAL INVESTIGATION.55

8.1 Summary of the clinical investigation organization...... 55

8.2 List of investigations...... 55

8.3 Name and address of sponsor...... 55

9 SIGNATURES PAGE...... 56

1 SUMMARY

1.1 Title of the clinical investigation

'USE OF THE ELECTROPHYSIOLOGICAL BIOFEEDBACK SYSTEM

EDUCTOR IN

  • STRESS DETECTION AND REDUCTION
  • MUSCULAR REEDUCATION
  • PAIN TREATMENT
  • PREGNANCY STABILITY IMBALANCE (DETECTION OF MEDICAL CONDITIONS)'

1.2 Introduction

The purpose of the clinical investigation is to evaluate the performance and tolerance of the procedures carried out with the Universal Electrophysiological Biofeedback System EDUCTOR in stress detection and reduction, muscular reeducation, pain treatment, assessed in patients with neuromuscular dystonia and muscle contractures and in detecting the medical conditions (pregnancy stability imbalance).

1.3 Demographic data of the patients

The demographic data of the 57 patients enrolled in this clinical investigation are:

Gender
Male
Female / 11(19,30%)
46(80,70%)
Average age / 61,81 years
Residence
Urban
Rural / 12(21,05%)
45(78,95%)
Profession
Pensioner
Worker
Home staying
Other / 41(71,93%)
3(5,26%)
3(5,26%)
10(17,55%)

In order to assess the effectiveness of the specific procedures carried out with the Universal Electrophysiological Biofeedback System EDUCTOR, the following parameters were monitored:

  • Score of depression, anxiety and stress of the subject (patient)
  • Score of neuromuscular dystonia
  • Intensity of the pain felt by the subject (patient), in case of dystonia and muscle contracture
  • Analysis of the incidence of all adverse events, including the overall impression regarding the success of the treatment
  • Analysis of the subject's perception on the extent to which the daily activities and the leisure time activities were restricted.

To assess the tolerance of the Universal Electrophysiological Biofeedback System EDUCTOR, its ease of use was also appreciated.

1.4 Results

The occurrence of the adverse phenomena and / or adverse events was not indicated in any patient, the use of the Universal Electrophysiological Biofeedback System EDUCTOR being safe, without causing the feeling of confusion after the procedure, vasovagal response (dizziness, sweating, etc.) or irritation of the skin, at the site of application of the electrodes.

The ease of use of the Universal Electrophysiological Biofeedback System EDUCTOR was appreciated by the physician investigator as being very good, the product being acceptable from the user's point of view.

Regarding the performance of the procedures carried out with the Universal Electrophysiological Biofeedback System EDUCTOR, we found the following:

  1. The procedures carried out with the Universal Electrophysiological Biofeedback System EDUCTOR in order to reduce the stress, depression and anxiety are extremely efficient and safe; the benefits for patient being represented on the one hand by the reduction improvement of depression, anxiety and reduction of stress, on the other hand, as a consequence, by the improvement of certain medical disorders, including the pain associated with them.
  1. The patients in the group receiving specific procedures carried out with the Biofeedback Universal System EDUCTOR, had a remarkable improvement of the health condition; the average score of dystonia, after making the procedures, decreased by 50%. Regarding the patients in the control group, at the end of the tracking period, the average score of dystonia decreased by 7%.
  1. After 6 specific procedures carried out with the Universal Electrophysiological Biofeedback System EDUCTOR, the average pain felt by patients decreased from the value of 6,2 Wong-Baker scale (pronounced pain, which determines the patient's inability to conduct some activities), to a value equal to 1,8 which means, according to the same scale, a pain which can be neglected. Therefore, after 6 procedures carried out with the Universal Electrophysiological Biofeedback System EDUCTOR, the patients were able to perform all daily activities, practically, without restrictions. Although the rate of decrease of the pain intensity was higher in the early days in the patients in the control group, later, it stagnated around the value 4 (moderate pain), while in the patients who received specific procedures carried out with the Universal Electrophysiological Biofeedback System EDUCTOR, the rate of decrease (although initially a little lower) was maintained; moreover, it widened, the pain decreasing significantly. The major benefits of using the Universal Electrophysiological Biofeedback System EDUCTOR consisted in significant improvement of the pain felt by the patients with muscular dystonia and / or with muscle contractures, when the procedures are associated with the standard treatment (physiotherapy, kinetic therapy, treatment with medication).
  1. In percentages, the medical conditions detected during the scan performed with the Biofeedback Electrophysiological Universal System, represent 33% of those detected by the standard medical investigations. With one exception, all medical conditions detected by scanning the human body were confirmed by the standard medical investigations: we appreciate that the Universal Electrophysiological Biofeedback System EDUCTOR is a very useful tool to guide the patients to the clinics for medical tests, recommending the investigations to be performed by it.
  1. There is a significant decrease in the restriction of the daily activities and the leisure time activities in the case of patients in the group which received specific procedures carried out by the Universal Electrophysiological Biofeedback System EDUCTOR, while in the patients in the control group, the largest share is represented by the patients who appreciated a stagnation of the restriction of activities.
  1. The Universal Electrophysiological Biofeedback System EDUCTOR is particularly effective in improving the condition of the patients, with positive influences on their quality of life.

1.5 Conclusions

The data collected after conducting the clinical investigation proved a particularly effectiveness of the Universal Electrophysiological Biofeedback System EDUCTOR in:

  • Detection and reduction of stress, depression and anxiety
  • Muscular re-education (improvement of the neuromuscular dystonia symptoms and of the muscle contractures)
  • Pain treatment
  • Detection of medical conditions

as well as safety of its use, no patient reported adverse phenomena / adverse events.

Initiation date of the clinical investigation: 22nd April 2015

Date of analysis: 29th May 2015.

2 INTRODUCTION

The Universal Electrophysiological Biofeedback System EDUCTOR is a 2nd class medical device, according to Directive 93/42/CEE, as amended by Directive 2007/47/EC, which fully meets the regulatory requirements, bearing the mark EC1868.

The clinical investigation was initiated in order to assess with a greater accuracy the performance and tolerability of the procedures carried out with the Universal Electrophysiological Biofeedback System EDUCTOR in stress detection and reduction, muscular re-education, pain treatment and in detection of the patients' medical conditions.

3. Biofeedback System EDUCTOR DEVICE AND METHODS

3.1 Description of the Universal Electrophysiological Biofeedback System EDUCTOR

The EUDCTOR device is a biofeedback electrophysiological universal system. The device coordinates a complex electro-modal of biofeedback with software for computer in order to obtain bioenergetic information from the patient's subconscious. The information is obtain through electrodes placed on the head, on the wrists and legs, which provide an accurate picture of the patient's general condition. The information is selected and listed by EDUCTOR in the order to the reaction scores and the stress factors are analysed during the session of stress reduction.

The Universal Electrophysiological Biofeedback System EDUCTOR uses low-frequency currents.

Its components are:

  • biofields transceiver, EDUCTOR;
  • electrodes / harness;
  • Cable to connect the device EDUCTOR to computer / LAPTOP;
  • a package of programs installed on a computer and a compatibility tester.

The Universal Electrophysiological Biofeedback System EDUCTOR detects the difference between the input and output signals of various frequencies and the associated computer program selects the standards (models) that are closest to the registration of the person. The measurements depend on the quality of the equipment, and the diagnostic's accuracy depends on the compliance with the statistical data (standards).

Principle of operation

Every organ and every cell has its own frequency or 'electromagnetic signature' and by collecting some huge amounts of data from thousands of patients, it could be found the normal frequencies for each organ. The viruses, bacteria and diseases specifically change the frequency of that organ, and thus, the device can diagnose fairly accurately. Also, the viruses, bacteria and pathogens have their own frequency (electromagnetic signature) and their presence in the body can thus be detected by the Universal Electrophysiological Biofeedback System EDUCTOR.

3.2 Clinical Investigation Plan

The main objectives of the clinical investigation conducted for the Universal Electrophysiological Biofeedback System EDUCTOR consist in the evaluation of its performance and tolerability in stress detection and reduction, muscular re-education, pain treatment and in detection of the subject's (patient's) medical conditions.

The clinical investigation was monocentric and comparative, performed on 4 groups of subjects, as follows:

  • A control group of 30 subjects with muscular dystonia / muscular contractures, which received the standard treatment;
  • A group of 27 subjects with muscular dystonia / muscular contractures, in addition to the standard therapy, received specific procedures carried out with the Universal Electrophysiological Biofeedback System EDUCTOR;
  • A control group of 14 subjects with gluteal muscle contracture (illness associated with muscle dystonia) which received the standard treatment;
  • A group of 14 subjects with gluteal muscle contracture (illness associated with muscle dystonia) which, in addition to the standard therapy, received specific procedures carried out with the Universal Electrophysiological Biofeedback System EDUCTOR.

It was conducted in compliance with ethical considerations and it was obtained the approval of the Ethics Commission attached to the National Institute of Recovery, Physical Medicine and Balneo- climatology of Bucharest.

The assurance of the data quality was carried out by auditing the clinical investigation by the sponsor's representatives, SC BIOFEEDBACK 2014 SRL, as well as by the monitor appointed by it, which verified the manner of storing and using the electrophysiological systems of biofeedback EDUCTOR during the investigation, but also the manner of collecting / registering and archiving the data taken during the evaluation of subjects by the physicians-investigators.

3.2.1 Subjects of the clinical investigation

The criteria for including the subjects in the clinical investigation were:

  • The acceptance of the subject by signing the consent form (BFK-ICF-01);
  • Age of the subject: between 18 and 75 years;
  • Subject with depression, anxiety, stress, muscular dystonia, muscle contracture;
  • Gender: male or female;
  • The non-inclusion of the subject in one of the exclusion criteria in the clinical investigation.

The criteria for excluding the subjects from the clinical investigation were:

  • Refusal of the subject to sign the consent form (BFK-ICF-01);
  • Subject belonging to the vulnerable populations;
  • Age of subject - less than 18 years;
  • Subject with concurrent conditions that could affect the evaluated parameters (listed above):

Epilepsy;

Patients with pacemaker;

Patients with electric hyper-reactivity;

Patients with skin diseases at the site of application of the electrodes;

  • Pregnant women;
  • Patients under the influence of drugs and alcohol;
  • Patients who received procedures carried out with bio-resonance devices in the last 4 weeks;
  • Insufficient cooperation of the subject;
  • The occurrence of events excluding the subject from the including criteria in the investigation.

3.2.2. Procedures carried out by subjects during the clinical investigation

During the clinical investigation, the subject were examined at the beginning of registration and during the investigation, concerning:

  • Subjects with muscular dystonia:

Score of depression, anxiety, stress;

Score of muscular dystonia;

Duration;

Pain felt;

Detection of other medical conditions.

  • Subjects with muscle contracture:

Score of depression, anxiety, stress;

Time period with that condition;

Localization;

Pain felt;

Detection of other medical conditions.

  • Overall impression regarding the success of the treatment;
  • Subject's perception on the extent to which the daily activities and the leisure time activities were restricted.

Later, after signing the informed consent, the patient received, in addition to the standard treatment, 6 specific procedures carried out with the Universal Electrophysiological Biofeedback System EDUCTOR, except for the patients in the control groups, who received only the standard treatment.

The choice of the type of procedure, depending on the medical condition which justified the inclusion of the subject in the medical investigation (procedure of scanning the body, specific procedures) was performed according to the user manual of the Universal Electrophysiological Biofeedback System EDUCTOR and according to the navigation manual, where it its detailed the operation manner of the device, together with the computer where the software Eductor64 is installed.

After the 6 procedures, the patients were assessed by the registration of the following parameters:

  • Subjects with muscular dystonia:

Score of depression, anxiety, stress;

Score of muscular dystonia;

Pain felt;

  • Subjects with muscle contracture:

Score of depression, anxiety, stress;

Time period with that condition;

Pain felt;

  • Overall impression regarding the success of the treatment;
  • Subject's perception on the extent to which the daily activities and the leisure time activities were restricted.

3.2.2 Treatment / simultaneous medication

The subjects included in this clinical investigation received the following treatments:

Subjects in the control group:

TREATMENT / SIMULTANEOUS MEDICATION PATIENTS IN THE CONTROL GROUP / TREATMENT / SIMULTANEOUS MEDICATION PATIENTS IN THE GROUP RECEIVING SPECIFIC PROCEDURES CARRIED OUT WITH THE DEVICE EDUCTOR
Nr. subject / initials / Treatment / medication / Nr. subject / initials / Treatment / medication
  1. GS
/ US, KT / 1. SM / US, KT
  1. PT
/ US, KT / 2. DN / IF,US
  1. PD
/ US, KT, Massage / 3. SAG / US, Parafin
  1. SA
/ US, KT, Massage / 4. MG / US, Magnetotherapy
  1. MM
/ US, Massage / 5. MV / US, Magnetotherapy
  1. AG
/ TENS, Augmentin / 6. NM / US, Magnetotherapy
  1. CP
/ US, KT, Massage, US, Magnetotherapy / 7. NG / US, Lasertherapy, Magnetotherapy
  1. CM
/ Massage, Paraffin / 8. IA / US, Parafin
  1. AE
/ US, KT, Massage / 9. SE / US, Parafin
  1. BE
/ KT, US, Magnetotherapy / 10. GT / US, Parafin
  1. IS
/ US, KT, Massage, Paraffin / 11. MM / US, Magnetotherapy
  1. GS
/ US, KT, Massage, Paraffin / 12. IC / US, KT
  1. TB
/ US, KT, Massage, Paraffin / 13. BF / US, Massage, Paraffin
  1. MG
/ US, KT, Massage / 14. VE / US, Lasertherapy,
  1. AE
/ US, Lasertherapy, Paraffin / 15. PV / US, Magnetotherapy
  1. DM
/ US, KT, Massage / 16. VA / US, TENS, Magnetotherapy
  1. MR
/ KT, US, Magnetotherapy / 17. MDD / US, KT
  1. IA
/ US, KT, Massage, Paraffin / 18. VT / US, KT, Lasertherapy
  1. DE
/ Lasertherapy, Massage / 19. NI / US, Magnetotherapy
  1. GE
/ US, Paraffin, US, Magnetotherapy / 20. ME / US, Lasertherapy,
  1. DF
/ US, KT, Massage, Paraffin / 21. PG / US, Massage, Paraffin
  1. DR
/ US, Massage, Lasertherapy / 22.BE / TENS, Paraffin, Lasertherapy
  1. IR
/ US, Parafin / 23. PEG / US, Lasertherapy,
  1. IF
/ US, Massage, Paraffin / 24. SG / US, Lasertherapy,
  1. BT
/ US, Massage / 25. VA1 / US, Massage, Paraffin
  1. VV
/ Massage, Paraffin / 26. OS / US, Massage
  1. SM
/ US, Massage / 27. MP / US, KT
  1. GS
/ US, KT, Massage
  1. BG
/ US, KT, Massage
  1. BM
/ US, KT, Massage, Paraffin

3.2.4. Duration of the subjects' evaluation

The subjects were evaluated for 2 weeks or until the performance of the 6 specific procedures, using the Universal Electrophysiological Biofeedback System EDUCTOR

3.2.5. Statistical analysis

Several null assumptions H01, H02… were taken into account, therefore:

H01 – depression, anxiety and stress of the subject after 6 specific procedures carried out with the device EDUCTOR; H01 = score equal to the one of the subjects in the control group, with the limit permissible error r1 = severe;

H02 – dystonia of the subject after 6 specific procedures carried out with the device EDUCTOR; H02 = score equal to the one of the subjects in the control group, with the limit permissible error r2 = severe;

H03 – pain felt by the subject before carrying out each specific procedure with the device EDUCTOR; H03 = severe pain, with the limit permissible error r3 = moderate;

H04 – overall impression regarding the success of the treatment, after 6 specific procedures carried out with the device EDUCTOR; H04 = 7, with the limit permissible error: r4 = 6;

H05 – extent to which the daily activities of the subject (patient) and his / her leisure time activities were restricted after 6 specific procedures carried out with the device EDUCTOR; H05 = 4, with the limit permissible error: r5 = 3;