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

NCT ID: NCT06178952

Last Updated: 2025-12-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

102 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-01-08

Study Completion Date

2027-01-31

Brief Summary

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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.

Detailed Description

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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 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 102 patients. 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, SF-36 and BI-PEM) is planned at later time points, specifically at 3 months post-stimulation, 6 months post-stimulation, 12 months post-stimulation, and 24 months post-stimulation.

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.

Important note: Originally, the study was designed as a multicenter study with the still-existing Austrian center (N=90) and an Italian center (N=30). Since study realization at the Italian center was ultimately not possible, the trial was streamlined to a single-center design. Consequently, enrollment at the Austrian center was refined so that at least 102 participants would reach the primary endpoint, thus meeting the original sample-size requirement. This administrative change was made prior to any analyses and does not affect the prespecified endpoints or procedures.

Conditions

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Post-COVID-19 Syndrome Fatigue

Keywords

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Transcranial Pulse Stimulation Post-COVID-19 Fatigue Non-invasive brain stimulation

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Prospective, double-blind, randomized, parallel group, placebo-controlled trial
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
All participants as well as the principal investigator, evaluating investigators, and the teams responsible for conducting stimulations, neuropsychological testing, and MR testing will be blinded. Specific individuals responsible for the organization of the study, who are neither involved in stimulation nor data collection, will not be blinded and will apply the verum or sham standoff device to the NEUROLITH system for a specific patient. As the stimulation team members won't have knowledge of the standoff device in use, they will remain completely blinded.

Study Groups

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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

Group Type EXPERIMENTAL

Transcranial pulse stimulation Verum

Intervention Type DEVICE

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 TPS

Participants will receive 5 Sham TPS sessions over a period of 10 days, with a singular daily session, each lasting approximately 30 minutes

Group Type SHAM_COMPARATOR

Transcranial pulse stimulation Sham

Intervention Type DEVICE

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.

Interventions

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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.

Intervention Type 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.

Intervention Type DEVICE

Eligibility Criteria

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Inclusion Criteria

* Signed written informed consent
* PCR-confirmed SARS-CoV-2 infection, laboratory confirmed antibody detection for SARS-CoV-2, or physician-verified COVID-19 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
* Relevant corticosteroid treatments administered within 6 weeks prior to the first application
* Tumor of the head if relevant for treatment
* Blood clotting disorders
* Participation in other studies
Minimum Eligible Age

20 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Medical University of Vienna

OTHER

Sponsor Role lead

Responsible Party

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Prof. Roland Beisteiner

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Roland Beisteiner, Prof.

Role: PRINCIPAL_INVESTIGATOR

Medical University of Vienna

Locations

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Medical University of Vienna

Vienna, Vienna, Austria

Site Status RECRUITING

Countries

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Italy Austria

Central Contacts

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Roland Beisteiner, Prof.

Role: CONTACT

Phone: +43/(0)1 40400-34080

Email: [email protected]

Michael Mitterwallner, Dr.

Role: CONTACT

Phone: +43 650 9626003

Email: [email protected]

Facility Contacts

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Roland Beisteiner, Prof.

Role: primary

Michael Mitterwallner, Dr.

Role: backup

References

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Other Identifiers

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102307161

Identifier Type: -

Identifier Source: org_study_id

102307161

Identifier Type: OTHER

Identifier Source: secondary_id