Transcranial Pulse Stimulation (TPS) in Post-COVID-19

January 8, 2024 updated by: Prof. Roland Beisteiner, Medical University of Vienna
The objective of the present study is to demonstrate treatment efficacy of transcranial pulse stimulation for patients with Post-COVID-19 related neurological symptoms (fatigue, cognitive deficits, mood deterioration). Fatigue, as measured by the Fatigue Impact Scale (FIS), will represent the primary outcome variable. The verum treatment will be compared to a sham (placebo) condition.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This clinical trial aims to investigate the treatment efficacy of transcranial pulse stimulation (TPS) using the NEUROLITH device (Storz Medical AG, Tägerwilen, Switzerland) in individuals with neurological post-COVID-19-symptoms. TPS is a novel brain stimulation therapy based on non-invasive ultrasound pulses and first published in 2019 by the Medical University of Vienna, Austria (Beisteiner et al. Advanced Science, 2019). The study employs a double-blind, randomized, placebo-controlled [multicenter-]* design with parallel groups (verum vs. sham). The anticipated timeframe for the entire study is 2 years, during which each participant is expected to be actively engaged for a period of 3-4 months. The aim is to include [120] patients, with 90 individuals participating in the Austrian center [and 30 in the Italian center]. The randomization ratio is 1:1, ensuring an even distribution between the verum (active treatment) and sham (placebo) groups. Three assessment points are scheduled (Baseline, PostStim, 1monthPostStim). Furthermore, to determine potential effects over time, limited data collection (involving only FIS, BDI-II, and SF-36) is planned at later time points, specifically at 3 months post-stimulation and 6 months post-stimulation (only at the Austrian center).

Hypotheses

  • H0: There is no significant difference in the effectiveness of transcranial pulse stimulation (TPS) and placebo treatment in improving primary and secondary endpoints.
  • H1: There is a significant difference in the effectiveness of transcranial pulse stimulation (TPS) and placebo treatment in improving primary and secondary endpoints.

Timeline

Each study participant will undergo the following sequence:

  1. Initial information session and clarification of relevant medical findings regarding inclusion and exclusion criteria

  2. Baseline screening:

    • 3-4 assessment sessions per patient within 14 days, including informed consent
    • Patients who do not meet the predefined cut-off values for BDI, FIS, and MoCA will be excluded from subsequent study phases

  3. Transcranial pulse stimulation

    • 5 stimulations per patient within 10 days
    • One stimulation per day lasting approximately 30 minutes.

  4. Post-stimulation assessment (PostStim)

    • Conducted during the week following brain stimulation
    • 2-3 assessment sessions per patient within 7 days

  5. One-month post-stimulation assessment (1monthPostStim)

    • Conducted one month after brain stimulation
    • 2-3 assessment sessions per patient within 7 days

Deviations of + 5 days from the intended timeline are considered tolerable.

Sample Size Calculation

The sample size calculation conducted with G*Power incorporated a small effect size (f = .10), α error probability of .05, and a power of 0.8, resulting in an estimate of 102 patients. While the consideration of a 12.5% drop-out rate from a previous study (Beisteiner et al., 2019) would yield a sample size of 114.75, a more conservative approach is being employed: To ensure sufficient participant numbers, the aim is to enroll 120 patients.

[Italian Center Adaptation: The Italian center will use the Austrian center as a template while considering available resources, potentially leading to a reduced number of data collection instruments and sessions per assessment point. After obtaining approval, this passage will be revised to include relevant information for the Italian center.]

[...]* indicates aspects of the planned multicenter design. The center in Italy is currently undergoing the approval process. Updates to this page will be made once confirmations are obtained.

Study Type

Interventional

Enrollment (Estimated)

120

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Signed written informed consent
  • PCR-confirmed SARS-CoV-2 infection
  • At least 12 months after initial SARS-CoV-2 infection that led to Post-COVID (subsequent SARS-CoV-2 infections are not a reason for exclusion)
  • Diagnosis of Post-COVID Syndrome or independent suspected diagnosis of Post-COVID Syndrome (Considering that physicians generally hesitate to provide clear-cut Post-COVID diagnoses, a tentative diagnosis by an independent general practitioner or a specialist in a field associated with Post-COVID will suffice for entering this study)
  • Age: 20-80
  • Evidence of a negative pregnancy test if medically adequate

Exclusion Criteria:

  • Clinically relevant realization of pre-COVID diseases with similar symptoms as Post-COVID
  • MoCA score <17 (cut-off for dementia)
  • BDI-II score ≥29 (cut-off for severe depression)
  • FIS <10 (cut-off for no fatigue)
  • Brain implants
  • Non-MR-compatible metal parts in the body
  • Metal parts in the head
  • Use of anticoagulants
  • Non-MR-compatible claustrophobia
  • Non-MR-compatible pacemaker
  • Pregnant and breastfeeding women
  • Clinically relevant history of surgery on the head, heart, or vessels
  • Corticosteroid treatments administered within 6 weeks prior to the first application
  • Cancer, tumor
  • Blood clotting disorders
  • Participation in other studies

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Verum TPS
Participants will receive 5 Verum TPS sessions over a period of 10 days, with a singular daily session, each lasting approximately 30 minutes
Device: Transcranial pulse stimulation Verum
Participants are slated to undergo a total of five TPS sessions over a 10-day interval. Each stimulation session will endure approximately 30 minutes and will be administered once daily.
Sham Comparator: Sham TPS
Participants will receive 5 Sham TPS sessions over a period of 10 days, with a singular daily session, each lasting approximately 30 minutes
Device: Transcranial pulse stimulation Sham
Placebo treatment will be performed using the same medical device, handpiece and treatment paradigm as in the verum treatment with one difference: the standoff device at the end of the handpiece. This device is designed to replicate the appearance, feel, and sound of the verum system, while omitting the transmission of any pulses.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Fatigue Impact Scale (FIS)
Time Frame: Baseline - 1 week after stimulation - 1 month after stimulation
The Fatigue Impact Scale (Fisk et al., 1994) is an instrument to measure the impact of fatigue symptoms. This self-report measure consists of 40 items divided into three subscales: cognitive functioning (10 items), physical functioning (10 items) and psychosocial functioning (20 items). In the validated German version, the statements are scored from 0-4 (0=never, 4=very often) leading to a total score of 0-160.
Baseline - 1 week after stimulation - 1 month after stimulation

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Beck Depression Inventory (BDI-II)
Time Frame: Baseline - 1 week after stimulation - 1 month after stimulation
The Beck Depression Inventory (BDI-II) is one of the most widely used instruments for measuring the severity of depression. It is a 21-item questionnaire for self-evaluation with 0-3 scores per item, ranging from 0 (normal state) to 63 (severe depression).
Baseline - 1 week after stimulation - 1 month after stimulation
Montreal Cognitive Assessment (MOCA)
Time Frame: Baseline - 1 week after stimulation - 1 month after stimulation
Montreal Cognitive Assessment (Nasreddine et al., 2005) is a clinical standard test for evaluating the following cognitive functions: visuospatial/executive, naming, memory, attention, language, abstraction, recall and orientation. The maximum score is 30 points.
Baseline - 1 week after stimulation - 1 month after stimulation
36-Item Short Form Health Survey (SF-36)
Time Frame: Baseline - 1 week after stimulation - 1 month after stimulation
The 36-item short-form health survey (Ware et al., 1992) is a widely used instrument to measure quality of life. The 36-item patient-reported survey covers eight health concepts including physical functioning (10 items), role limitations due to physical health (4 items), role limitations due to emotional problems (3 items), energy/fatigue (4 items), emotional well-being (5 items), social functioning (2 items), pain (2 items), and general health (5 items). All questions are scored on a scale from 0 (worst health) to 100 (best health).
Baseline - 1 week after stimulation - 1 month after stimulation
Trail Making Test A and B (TMT-A and TMT-B)
Time Frame: Baseline - 1 week after stimulation - 1 month after stimulation
The Trail Making Test (Reitan et al., 1958) consist of two parts A and B. For each part, patients need to fulfill a task by connecting letters and/or numbers in the right way. The scoring of both parts is done by taking the time required to complete them.
Baseline - 1 week after stimulation - 1 month after stimulation
Positive and Negative Affect Schedule (PANAS)
Time Frame: Baseline - 1 week after stimulation - 1 month after stimulation
The Positive and Negative Affect Schedule (Watson et al., 1988) is an instrument to assess mood, specifically distinguishing between positive and negative affect. It has two subscales (positive and negative) and consists out of 20 items which are scored using a 5-point scale (1= not at all - 5 = extremely).
Baseline - 1 week after stimulation - 1 month after stimulation
Beck Anxiety Inventory (BAI)
Time Frame: Baseline - 1 week after stimulation - 1 month after stimulation
The Beck Anxiety Inventory (Beck et al., 1988) is a self-reported scale to measure anxiety. It consists of 21 items, which are scored from 0-3. The BAI has a total range from 0 to 63.
Baseline - 1 week after stimulation - 1 month after stimulation
Six Minute Walking Test (6MWT)
Time Frame: Baseline - 1 week after stimulation - 1 month after stimulation
The six-minute walking test, developed by the American Thoracic Society 2002, is an exercise test to assess aerobic capacity and endurance. The patients are asked to walk as far as they can within 6 minutes. Subjective tests (Borg-Scale, 0-10) will be administers before and after walking.
Baseline - 1 week after stimulation - 1 month after stimulation
Test of Attentional Performance (TAP)
Time Frame: Baseline - 1 week after stimulation - 1 month after stimulation
The Test of Attentional Performance (Zimmermann et al., 2002) is an instrument to measure attentional function. There are 14 subscales, including Sustained Attention, Vigilance, and Divided Attention. It will be carried out digitally using the TAP software package.
Baseline - 1 week after stimulation - 1 month after stimulation
Verbal Learning and Memory Test (VLMT)
Time Frame: Baseline - 1 week after stimulation - 1 month after stimulation
The German version of the Verbal Learning Memory Test by Helmstaedter and colleagues (2001) is an instrument to measure different parameters of declarative verbal memory such as learning or recognition performance. It consists of a learning phase, in which patients need to learn two lists of 15 words each, a delayed recall and a recognition test.
Baseline - 1 week after stimulation - 1 month after stimulation
Stroop color word test (STROOP)
Time Frame: Baseline - 1 week after stimulation - 1 month after stimulation
The Stroop Color-Word Test (Stroop, 1935) is a useful and reliable psychological assessment tool (Lezak, Howieson, & Loring, 2004) that measures a person's ability to inhibit an automatic response in favor of an atypical one. Specifically, it involves identifying the ink color of incongruously labeled color words (van Boxtel et al., 2001). The test can measure cognitive performance functions such as naming speed, selectivity, and alertness (Bäumler & Stroop, 1985).
Baseline - 1 week after stimulation - 1 month after stimulation
Satisfaction With Life Scale (SWLS)
Time Frame: Baseline - 1 week after stimulation - 1 month after stimulation
The SWLS (Satisfaction with Life Scale), developed by Diener and colleagues (1985), is a widely used self-report questionnaire designed to measure individuals' subjective satisfaction with their own lives. It consists of five items that capture different aspects of life satisfaction.
Baseline - 1 week after stimulation - 1 month after stimulation
Somatization subscale of the Symptom Check List-90-R (SCL-90-R SOM)
Time Frame: Baseline - 1 week after stimulation - 1 month after stimulation
The SCL-90-R (Schmitz et al., 2000) is a 90-item self-report symptom inventory used in clinical and research settings to evaluate psychological symptoms and distress. Only the SOM (Somatization) subscale within the SCL-90-R will be used for the present study. It consists of 12 items on a 5-point Likert scale that assess physical symptoms. The maximum score for the subscale is 48 points.
Baseline - 1 week after stimulation - 1 month after stimulation
Post-Exertional Malaise (BI-PEM)
Time Frame: Baseline - 1 week after stimulation - 1 month after stimulation
The German version of the DSQ PEM questionnaire (Cotler et al., 2018; Jason & Sunnquist, 2018) comprises three subscales and a total of 11 items, focusing on post-exertional malaise. The subscales include questions concerning frequency, severity and duration of the symptoms after engaging in activities over the past 6 months.
Baseline - 1 week after stimulation - 1 month after stimulation
Neuroimaging
Time Frame: Baseline - 1 week after stimulation - 1 month after stimulation
Magnetic resonance imaging (MRI) will be recorded the week before, the week after and 1 month after TPS stimulations by center 1 (Vienna) for the Austrian study population. MR measurements will be performed using a 3 T SIEMENS PRISMA MR with a 64-channel head coil. MRI images will be obtained to assess changes in structural and functional brain connectivity.
Baseline - 1 week after stimulation - 1 month after stimulation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Medical University of Vienna

Collaborators

Campus Bio-Medico University

Investigators

  • Principal Investigator: Roland Beisteiner, Prof., Medical University of Vienna

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 8, 2024

Primary Completion (Estimated)

January 1, 2026

Study Completion (Estimated)

January 1, 2026

Study Registration Dates

First Submitted

December 20, 2023

First Submitted That Met QC Criteria

December 20, 2023

First Posted (Actual)

December 21, 2023

Study Record Updates

Last Update Posted (Actual)

January 9, 2024

Last Update Submitted That Met QC Criteria

January 8, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 102307161 (Other Identifier: BASG (Austrian Agency for Health and Food Safety))

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Due to the sensitive nature of the medical information used in the study, access to individual data will not be provided to other researchers.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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