Radiofrequency Intervention in Post COVID-19 Patients

Covid19 Clinical Trial

Official title:

Radiofrequency Intervention in Neurological, Pneumological and Musculoskeletal Pathologies Post COVID-19

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04920890
• Other study ID #: ART-GLB-RF-COVID
• Status: Recruiting
• Phase: N/A
• Start date: June 16, 2021
• Est. completion date: July 20, 2022

Study information

• Verified date: May 2022
• Source: Clinica Gema Leon
• Contact: Gema León Bravo, Fisioterapia
• Phone: (+34) 667 40 11 16
• Email: gemafisio[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The sequelae that occur in post-COVID-19 patients are multiple and, at a therapeutic level, these represent a new challenge within the general context of the pandemic that the world is suffering.

The virus has managed to end thousands of lives today and many other cases are being charged as directly responsible for a multiplicity of multi-system damages that need to be diagnosed and treated. Among the most relevant, are those that can affect to neurological, respiratory and musculoskeletal levels in patients without previous pahologies, and in patients at risk who already had a pathology prior to infection.

On the other hand, signs and symptoms have been observed characteristic in the organ systems described above in post-contagion patients, directly associated with sequelae SARV-CoV2. The radio frequency (RF) of electromagnetic waves represents a technology of proven efficacy and safety in multiple fields of both human and veterinary medicine. These include neurological and pneumological pathologies, and very especially those that affect the locomotor system. In therapeutics there are different RF modalities depending on the modality, polarity, type of signal and frequency, which in turn translate into different therapeutic profiles, clinical indications, efficacy and safety.

Among the RF technologies most used today and that have a greater scientific background, is the one known as Resistive Capacitive Monopolar Radio Frequency at 448 kHz (INDIBA®) (RFMCR). This study aims to assess the efficacy and safety of RFMCR in the treatment of neurological, respiratory and musculoskeletal sequelae in patients presenting this type of pathologies that appear after contagion by COVID-19. Through this non-invasive technique, the investigators want to show that RF can help the physical rehabilitation of these patients through metabolic stimulation, increased vascularization and oxygenation of directly affected tissues, effects of deep hyperthermia generated by the interaction of the current with the treated biological substrate, as well as the activation of tissue regeneration, the result of subthermal action. It is thus intended to improve signs such as lung capacity, dyspnea, neuropathies and global muscle capacity, which are essential for the recovery of the post-COVID-19 patients.

The hypothesis of this study is that current post-COVID-19 treatments can be significantly improved in order to prevent complications and ensure the patients' well-being.

Description:

The new post-pandemic era has left sequelae in patients who presented the signs and symptoms of SARS-CoV-2 and subsequently faced a positive for COVID-19. Such sequelae will be evident at various systemic levels of the affected patienta in the short, medium and long term future. One of these levels is neurological, respiratory and musculoskeletal complications and injuries that have been documented throughout all scientific research since the beginning of massive infections worldwide.

SARS-CoV-2 is transmitted by penetrating the respiratory route (mostly), by fluid contact, and to a lesser extent, through the ocular pathway. In the field of neurology, pulmonology and the musculoskeletal system, different forms of RF, nerve infiltrations, lymph node injuries, plantar fasciitis, spinal (peripheral) nerve disorders, etc. have been documented.

If the investigators focus on one of the most prevalent symptoms (those that affect the respiratory system), the bibliography that endorses that the RFMCR could improve has been referenced.

In 1992, Martínez Rubio and Bordas described how, from the first treatment session, 60% of asthmatic patients treated (n = 52) improved significantly, both in terms of bronchospasm and dyspnea. In general, 5 to 10 sessions were necessary to improve symptoms in more than 75% of patients. In 2020, Bito et al. published how the use of this technology significantly increases chest wall motility in older women (74.6 ± 5.4 years on average; n = 28). These symptomatic effects can be correlated with the findings of Tashiro et al., which proved that 15 minutes of treatment at the epigastric level significantly increased (p <0.016) the levels of total hemoglobin (Hb) and oxy-Hb, and how this significant increase, was maintained at least up to 30 minutes after the end of the treatment (at which time measurement was interrupted). These findings reinforce those described by Bito et al. and those of Yokata et al.

No less important are the proven effects of hyperthermia in strengthening the immune system both in healthy patients (prevention) and in patients with infectious diseases.

The aim of this study is to assess the potential benefits of RFMCR in patients with neurological, respiratory and/or musculoskeletal problems which started after SARV-CoV-2 infection. The work proposed here aims to demonstrate the advantages of establishing RF as an excellent treatment for post-COVID-19 sequelae, due to its ability to reinforce immune action, modulate the inflammatory response and activate cellular and tissue regeneration.

The specific objectives of this research work are:

1. To demonstrate the efficacy of RFMCR as a therapy in neurological, respiratory and musculoskeletal pathologies derived from the sequelae of COVID-19.

2. To evidence and document the effects generated by the treatment with RFMCR in such systems.

3. To estimate the level of benefit from RF in each of the different systems treated and define the benefit/risk ratio.

4. To present and validate the therapy for the injuries under study that show significant improvements.

REGULATIONS

1. This clinical study will be carried out in accordance with the protocol, the principles established in the current revised version of the Declaration of Helsinki (Fortaleza, 2013) and in accordance with the applicable regulatory requirements.

2. The researcher is aware, when signing the protocol, of the obligation to adhere to the instructions and procedures described in it, and will ensure that the established provisions are strictly adhered to.

3. The study will not begin until the approval of the Research Ethics Committee has been obtained.

4. The principal investigator is responsible for ensuring that this protocol, the informed consent document, and any other information that is presented or facilitated to the possible subjects is reviewed and approved by the CEI. The Researcher agrees to allow direct access to the REC to all relevant documents.

INFORMED CONSENT.

5. In this case, patients must give their consent prior to being included in the study. The content and the procedure for obtaining it must be in accordance with all applicable legal requirements.

6. The investigator is responsible for obtaining the written informed consent of each patient participating in this study, after having explained in an understandable way, the nature, objectives, methods, expected benefits and possible risks of the study. The investigator must also explain to them that patients are completely free to refuse to participate in the study or to withdraw from it at any time, for whatever reason.

7. The study patients will give their consent, signing the corresponding model. For this purpose, each informed consent must be signed by both the investigator and the patient.

CONFIDENTIALITY.

8. All information related to the study is considered confidential in compliance with the confidentiality and custody of the data collected, in accordance with the 3/2018 Law on the protection of personal data (LOPDGDD), (article 5). Article 5.1 .f) of the RGPD states that personal data will be treated in such a way as to guarantee confidentiality and integrity

9. In order to guarantee the confidentiality of the study data, only the main researcher and her team of collaborators will have access to it, the CEI and the pertinent health authorities.

FINANCING

1. The financing is assumed by the Gema León Physiotherapy and Rehabilitation Clinic. There is no direct economic consideration for this, although there is a dedication of time and work by the team of physiotherapists (social security, payroll, personal income tax, etc.) that is not economically remunerated and is assumed or absorbed this way. In addition, the RFMCR technology (equipment and accessories) will be provided by the company INDIBA S.A., through a temporary assignment without any financial compensation either from the Gema León Physiotherapy Clinic, or from any patient. The treatment of these is completely free for them.

2. The patient must travel to the clinic facilities and it is the researcher who will be responsible for the treatment in it.

3. No difficulties are foreseen in its performance since it will be carried out using a schedule adapted to the patient that allows the study to be monitored.

It is intended to carry out a longitudinal study with the participation of 98 patients for each type of pathology neurological, respiratory and musculoskeletal, who confirmed a positive test for COVID-19. Thus, the entire population was 294 patients. The sample size for our study is large enough to detect a clinically important difference in the primary outcome (s). For this, the investigators reviewed references at the bibliographic level, in which paired studies obtained a statistically significant value, being able to support our study. If the sample size was insufficient but statistically significant, the investigators would resort to expanding the sample. The division of the sample is carried out at random within the established groups.

The patients will be divided INTO TTHREE GROUPS: Group A, or placebo of 33 participants for each pathology modality, evaluated and administered false treatment with the machine turned off.This group will be divided into 3 subgroups: Placebo" with neurological A1, respiratory A2 and/or musculoskeletal pathologies A3, acquired after COVID-19 ; group B or group of treatment with RF and manual therapy. This group will be divided into 3 subgroups of 34 participants each: Group B1 "Neurological Pathologies after COVID-19" and positive in COVID-19 with RF treatment y manual therapy; Group B2 "Respiratory Pathologies after COVID-19" and positive in COVID-19 with RF treatment and manual therapy and Group B3 "Musculoskeletal Pathologies after COVID-19" and positive in COVID-19 with RF treatment and manual therapy. Finally Group C of 31 participants each: Group C1 "Neurological Pathologies after COVID-19" and positive in COVID-19 with manual therapy; Group C2 "Respiratory Pathologies after COVID-19" and positive in COVID-19 with manual therapy and Group C3 "Musculoskeletal Pathologies after COVID-19" and positive in COVID-19 with manual therapy.

Thus we compare the therapies of groups A1, B1 and C1, of Neurological Pathologies. Then we compare the therapies of groups A2, B2 and C2, of Respiratory Pathologies.

And Finally we compare the therapies of groups A3, B3 and C3, of Musculoskeletal Pathologies.

All groups will be evaluated at the beginning, a second evaluation after 3 weeks and a third final control after 12 sessions. A fourth evaluation will be carried out after the last and final evaluation, 6 weeks after finishing the treatment. Each of the participants will be informed of the study, the objective, its possible benefits and the side effects that could arise. A) Therefore, each patient must give their free and confirmed consent through signature. Among the items in the methodology, the following stand out:

Primary data parameters: A series of questions will be asked to each of the patients about the conditions diagnosed during the disease and those suffered after the infection that are directly related to abnormalities to be assessed.

Secondary Data Parameters: The therapeutic protocol will be executed in the facilities of the Gema León Physiotherapy and Rehabilitation Clinic (Cordoba, Spain). Such RF therapeutic protocol will be implemented by application with an INDIBA® Activ device, whose function is to reduce inflammation, stimulate immunity and promote tissue regeneration. This will consist of a 30-minute treatment, composed by 5 minutes of treatment with the capacitive electrode and 25 minutes of the resistive electrode. A total of 12 sessions will be scheduled (two per week), and all processes will be documented from the beginning of therapy (the resources used will be provided by INDIBA and the Gema León Physiotherapy and Rehabilitation Clinic, whose supervision will be carried out by the direction of both).

Dependent Variables: variables of nominal type such as sex, age, vaccination, number of days with symptoms, type of symptom will be created. The patients will be grouped into 3 groups of 98 participants each (294 in total):

• Group A "Control" without pathologies neurological, respiratory and/or musculoskeletal previous and positive confirmed in test carried out without protocol of RF wave treatment or Placebo: with Neurological Pathologies after COVID-19 or A1, Respiratory Pathologies after COVID-19 or A2 and Musculoskeletal Pathologies after COVID-19 or A3, acquired after COVID-19.

• Group B or group of treatment with RF and manual therapy: Group B1 "Neurological Pathologies after COVID-19". Group B2 "Respiratory Pathologies after COVID-19". Group B3 "Musculoskeletal Pathologies after COVID-19" (these last three subgroups being group B of treatment with RFMCR, INDIBA® Activ" and manual therapy.

• Group C or group of treatment with manual therapy only: Group C1 "Neurological Pathologies after COVID-19" and positive in COVID-19 with manual therapy; Group C2 "Respiratory Pathologies after COVID-19" and positive in COVID-19 with manual therapy and Group C3 "Musculoskeletal Pathologies after COVID-19" and positive in COVID-19 with manual therapy.

Independent Variables: In order to compare the variables between groups, different methods of pain threshold and function of the mentioned systems will be used, such as: Global Functionality Scale (GAF), Katz Index for Independence, Lawton and Brody Scale of Basic Activities, Barthel index for disability, European Quality of Life 5-D Questionnaire (EURO- QoL 5-D) for quality of life, Tinetti test for gait and balance, joint amplitude scale measured with the goniometer (goniometry), strength muscle dynamometer (Dynamometry), pain index (Visual Analogue Scale (VAS), Ashworth Scale modified for spasticity, reflectivity measurement with the Wartenberg Scale for bone tendon reflexes (ROTs), examination of sensitivity from evaluation of dermatomes, measurement of lung function with spirometry, tests for respiratory muscle function (measurement of inspiratory and expiratory pressures maximum; Pimax and Pemax, respectively), and Sadoul scale for dyspnea and measurement of costal excursion. The statistical analysis is based on variables of nominal type mostly, which are suitable for the Chi square test with a significance value of 95% for the results (p <0.05). However, if there are numerical data that must be compared between groups, the analysis will be used for ANOVA test with the same significance value for the comparison between results.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 294
• Est. completion date: July 20, 2022
• Est. primary completion date: June 21, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Having passed the covid-19 disease without any previos pathology.

Exclusion Criteria:

• Having passed the covid-19 disease with previous pathology, or not having passed the covid-19 disease.

Related Conditions & MeSH terms

• COVID-19
• Covid19
• Musculoskeletal Injury
• Neurological Injury
• Respiratory Injury
• Trauma, Nervous System
• Wounds and Injuries

Intervention

Device:
• Radiofrequency therapy with manual therapy
Monopolar Capacitive Resistive Radio Frequency at 448 kHz (INDIBA®) (RFMCR) with manual therapy.
• Placebo without radiofrequency.
The device will be used without turning on the patient, thus administering a placebo treatment.

Other:
• Manual therapy.
Common manual therapy administered for said pathology by traditional physiotherapy.

Locations

Country	Name	City	State
Spain	Gema León Physiotherapy and Rehabilitation Clinic	Córdoba	Andalucía

Sponsors (1)

Lead Sponsor	Collaborator
Clinica Gema Leon

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Functionality (independence of the patient): Katz.	Minimum value: 0 (ability to perform basic daily activities). Maximum value: 1 (inability to perform basic daily activities). Optimal value: 0.	3 months
Primary	Quality of life related to health, according to the Euro-Qol 5D scale.	Questionaire with two parts: Descriptive system (5 items). Minimum value: 1 (absence of dificulties). Maximum value: 3 (plenty of difficulties). Optimal value: 1.; Visual analogical scale (EVA). Minimum value: 0 (worst imaginable state of health). Maximum value: 100 (best imaginable state of health). Optimal value: 100.	3 months
Primary	Functionality: Lawton and Brody.	Minimum value: 0 (dependent patient). Maximum value: 1 (independent patient). Optimal value: 1.	3 months
Primary	Functionality (ability to perform basic daily activities): Barthel	Minimum value: 0 (completely dependent patient). Maximum value: 100 (completely independent patient). Optimal value: 100.	3 months
Secondary	Range of motion	Neurological evaluation	3 months
Secondary	Strength: dynamometry.	Neurological evaluation	3 months
Secondary	Sensitivity evaluation: pain (puncture).	ASIA scale. Minimum value: 0 (complete absence of sensitivity). Maximum value: 2 (normal). Optimal value: 2.	3 months
Secondary	Reflectivity: Osteotendinous reflexes (Neurological evaluation)	Minimum value: 0 (absence of reflexes). Maximum value: 4 (hyperreflexia (hyperactivity with clonus)). Optimal value: 2 (normal reflectivity).	3 months
Secondary	Balance: Tinetti (Neurological evaluation)	Minimum value: 0 (complete absence of balance and functionality). Maximum value: 16 (highest grade of balance and functionality). Optimal value: 16.	3 months
Secondary	Tone (spasticity) : Modified Asworth (Neurological evaluation)	Minimum value: 0 (normal muscular tone). Maximum value: 4 (extreme hypertonia). Optimal value: 0.	3 months
Secondary	Motion range.	Musculoskeletal evaluation	3 months
Secondary	Strength (dynamometry).	Musculoskeletal evaluation	3 months
Secondary	Intensity of pain: Visual Analogical Evaluation (EVA)	Minimum value: 0 (absence of pain). Maximum value: 10 (unbearable pain). Optimal value: 0.	3 months
Secondary	Expandability of the rib cage in cm (respiratory evaluation).	Three thoracometries: axilary or superior, middle or xiphoid and inferior or costal.	3 months
Secondary	Sadoul's dyspnea rating scale (Respiratory evaluation)	Minimum value: 0 (absence of dyspnea). Maximum value: 5 (dyspnea occurs with minimal efforts). Optimal value: 0.	3 months
Secondary	Respiratory muscle function: Muscle pressures with mouthpiece connected to manometer (Pimax and Pemax)	Respiratory evaluation	3 months
Secondary	Tactile sensitivity evaluation (soft touch).	ASIA scale. Minimum value: 0 (complete absence of sensitivity). Maximum value: 2 (normal). Optimal value: 2.	3 months