Post-COVID-19 SyndromeNCT06178952
Transcranial Pulse Stimulation (TPS) in Post-COVID-19
A study testing Transcranial pulse stimulation Verum in people with Post-COVID-19 Syndrome and Fatigue, run by Medical University of Vienna at 1 site in Austria.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 20 to 80 years
- Conditions the study is for
- Post-COVID-19 Syndrome, Fatigue
- What is being tested?
- Transcranial pulse stimulation Verum
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 102 participants
- Where
- 1 siteAustria
- Study dates
- 8 Jan 2024to Jan 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 16Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Austria1 site, 1 recruiting
- Recruiting
Medical University of Vienna
Vienna, State of Vienna, 1090
Roland Beisteiner, Prof., +43/(0)1 40400-34080, roland.beisteiner@meduniwien.ac.at
Michael Mitterwallner, Dr., +43 650 9626003, michael.mitterwallner@meduniwien.ac.at
About this study
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.
Read the 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 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:
- Initial information session and clarification of relevant medical findings regarding inclusion and exclusion criteria
- 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
- Transcranial pulse stimulation
- 5 stimulations per patient within 10 days
- One stimulation per day lasting approximately 30 minutes.
- Post-stimulation assessment (PostStim)
- Conducted during the week following brain stimulation
- 2-3 assessment sessions per patient within 7 days
- 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
- Post-COVID-19 Syndrome, Fatigue
- Being tested
- Transcranial pulse stimulation Verum, Transcranial pulse stimulation Sham
- Keywords
- Transcranial Pulse Stimulation, Post-COVID-19, Fatigue, Non-invasive brain stimulation
- Medical subject headings
- Post-Acute COVID-19 Syndrome, Fatigue
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcranial pulse stimulation VerumDevice
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.
Transcranial pulse stimulation ShamDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| Verum TPS | Experimental | Participants will receive 5 Verum TPS sessions over a period of 10 days, with a singular daily session, each lasting approximately 30 minutes Receives: Device: Transcranial pulse stimulation Verum |
| Sham TPS | Sham comparator | Participants will receive 5 Sham TPS sessions over a period of 10 days, with a singular daily session, each lasting approximately 30 minutes Receives: Device: Transcranial pulse stimulation Sham |
What is being measured
The primary outcome is the main question the study is designed to answer.
Fatigue Impact Scale (FIS)
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.
Measured: Baseline - 1 week after stimulation - 1 month after stimulation
Secondary outcomes (14)
Beck Depression Inventory (BDI-II)
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).
Measured: Baseline - 1 week after stimulation - 1 month after stimulation
Montreal Cognitive Assessment (MOCA)
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.
Measured: Baseline - 1 week after stimulation - 1 month after stimulation
36-Item Short Form Health Survey (SF-36)
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).
Measured: Baseline - 1 week after stimulation - 1 month after stimulation
Trail Making Test A and B (TMT-A and TMT-B)
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.
Measured: Baseline - 1 week after stimulation - 1 month after stimulation
Positive and Negative Affect Schedule (PANAS)
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).
Measured: Baseline - 1 week after stimulation - 1 month after stimulation
Beck Anxiety Inventory (BAI)
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.
Measured: Baseline - 1 week after stimulation - 1 month after stimulation
Six Minute Walking Test (6MWT)
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.
Measured: Baseline - 1 week after stimulation - 1 month after stimulation
Test of Attentional Performance (TAP)
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.
Measured: Baseline - 1 week after stimulation - 1 month after stimulation
Verbal Learning and Memory Test (VLMT)
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.
Measured: Baseline - 1 week after stimulation - 1 month after stimulation
Stroop color word test (STROOP)
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).
Measured: Baseline - 1 week after stimulation - 1 month after stimulation
Satisfaction With Life Scale (SWLS)
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.
Measured: Baseline - 1 week after stimulation - 1 month after stimulation
Somatization subscale of the Symptom Check List-90-R (SCL-90-R SOM)
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.
Measured: Baseline - 1 week after stimulation - 1 month after stimulation
Post-Exertional Malaise (BI-PEM)
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.
Measured: Baseline - 1 week after stimulation - 1 month after stimulation
Neuroimaging
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.
Measured: Baseline - 1 week after stimulation - 1 month after stimulation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Dec 2023
- Study start8 Jan 2024
- Primary completionJan 2027 (estimated)
- Study completionJan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (19)Papers the sponsor has linked to this study.
- Other trials for Post-COVID-19 SyndromeStudies of the same condition, open and under way.
- More trials run by Medical University of ViennaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Prospective, double-blind, randomized, parallel group, placebo-controlled trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 102 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Medical University of Vienna
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Prof. Roland Beisteiner, Medical University of Vienna
- Investigators
- Roland Beisteiner, Prof., Principal investigator, Medical University of Vienna
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06178952
- Sponsor's protocol ID
- 102307161
- Other IDs
- 102307161
- Status last verified
- Dec 2025
- First submitted
- 20 Dec 2023
- Last updated
- 23 Dec 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No: Due to the sensitive nature of the medical information used in the study, access to individual data will not be provided to other researchers.
Publications
Beisteiner R, Matt E, Fan C, Baldysiak H, Schonfeld M, Philippi Novak T, Amini A, Aslan T, Reinecke R, Lehrner J, Weber A, Reime U, Goldenstedt C, Marlinghaus E, Hallett M, Lohse-Busch H. Transcranial Pulse Stimulation with Ultrasound in Alzheimer's Disease-A New Navigated Focal Brain Therapy. Adv Sci (Weinh). 2019 Dec 23;7(3):1902583. doi: 10.1002/advs.201902583. eCollection 2020 Feb.
PubMed 32042569Beisteiner R, Hallett M, Lozano AM. Ultrasound Neuromodulation as a New Brain Therapy. Adv Sci (Weinh). 2023 May;10(14):e2205634. doi: 10.1002/advs.202205634. Epub 2023 Mar 24.
PubMed 36961104Cont C, Stute N, Galli A, Schulte C, Logmin K, Trenado C, Wojtecki L. Retrospective real-world pilot data on transcranial pulse stimulation in mild to severe Alzheimer's patients. Front Neurol. 2022 Sep 14;13:948204. doi: 10.3389/fneur.2022.948204. eCollection 2022.
PubMed 36188380Douaud G, Lee S, Alfaro-Almagro F, Arthofer C, Wang C, McCarthy P, Lange F, Andersson JLR, Griffanti L, Duff E, Jbabdi S, Taschler B, Keating P, Winkler AM, Collins R, Matthews PM, Allen N, Miller KL, Nichols TE, Smith SM. SARS-CoV-2 is associated with changes in brain structure in UK Biobank. Nature. 2022 Apr;604(7907):697-707. doi: 10.1038/s41586-022-04569-5. Epub 2022 Mar 7.
PubMed 35255491Ashraf N, Abou Shaar B, Taha RM, Arabi TZ, Sabbah BN, Alkodaymi MS, Omrani OA, Makhzoum T, Almahfoudh NE, Al-Hammad QA, Hejazi W, Obeidat Y, Osman N, Al-Kattan KM, Berbari EF, Tleyjeh IM. A systematic review of trials currently investigating therapeutic modalities for post-acute COVID-19 syndrome and registered on WHO International Clinical Trials Platform. Clin Microbiol Infect. 2023 May;29(5):570-577. doi: 10.1016/j.cmi.2023.01.007. Epub 2023 Jan 13.
PubMed 36642173Han Q, Zheng B, Daines L, Sheikh A. Long-Term Sequelae of COVID-19: A Systematic Review and Meta-Analysis of One-Year Follow-Up Studies on Post-COVID Symptoms. Pathogens. 2022 Feb 19;11(2):269. doi: 10.3390/pathogens11020269.
PubMed 35215212Kubota T, Kuroda N, Sone D. Neuropsychiatric aspects of long COVID: A comprehensive review. Psychiatry Clin Neurosci. 2023 Feb;77(2):84-93. doi: 10.1111/pcn.13508. Epub 2022 Dec 12.
PubMed 36385449Linnhoff S, Koehler L, Haghikia A, Zaehle T. The therapeutic potential of non-invasive brain stimulation for the treatment of Long-COVID-related cognitive fatigue. Front Immunol. 2023 Jan 9;13:935614. doi: 10.3389/fimmu.2022.935614. eCollection 2022.
PubMed 36700201Matt E, Kaindl L, Tenk S, Egger A, Kolarova T, Karahasanovic N, Amini A, Arslan A, Saricicek K, Weber A, Beisteiner R. First evidence of long-term effects of transcranial pulse stimulation (TPS) on the human brain. J Transl Med. 2022 Jan 15;20(1):26. doi: 10.1186/s12967-021-03222-5.
PubMed 35033118Matt E, Dorl G, Beisteiner R. Transcranial pulse stimulation (TPS) improves depression in AD patients on state-of-the-art treatment. Alzheimers Dement (N Y). 2022 Feb 10;8(1):e12245. doi: 10.1002/trc2.12245. eCollection 2022.
PubMed 35169611O'Sullivan O. Long-term sequelae following previous coronavirus epidemics. Clin Med (Lond). 2021 Jan;21(1):e68-e70. doi: 10.7861/clinmed.2020-0204. Epub 2020 Nov 3.
PubMed 33144403Pinzon RT, Wijaya VO, Jody AA, Nunsio PN, Buana RB. Persistent neurological manifestations in long COVID-19 syndrome: A systematic review and meta-analysis. J Infect Public Health. 2022 Aug;15(8):856-869. doi: 10.1016/j.jiph.2022.06.013. Epub 2022 Jun 23.
PubMed 35785594Popescu T, Pernet C, Beisteiner R. Transcranial ultrasound pulse stimulation reduces cortical atrophy in Alzheimer's patients: A follow-up study. Alzheimers Dement (N Y). 2021 Feb 25;7(1):e12121. doi: 10.1002/trc2.12121. eCollection 2021.
PubMed 33681449Radjenovic S, Dorl G, Gaal M, Beisteiner R. Safety of Clinical Ultrasound Neuromodulation. Brain Sci. 2022 Sep 22;12(10):1277. doi: 10.3390/brainsci12101277.
PubMed 36291211Santana K, Franca E, Sato J, Silva A, Queiroz M, de Farias J, Rodrigues D, Souza I, Ribeiro V, Caparelli-Daquer E, Teixeira AL, Charvet L, Datta A, Bikson M, Andrade S. Non-invasive brain stimulation for fatigue in post-acute sequelae of SARS-CoV-2 (PASC). Brain Stimul. 2023 Jan-Feb;16(1):100-107. doi: 10.1016/j.brs.2023.01.1672. Epub 2023 Jan 21.
PubMed 36693536
Study at a glance
From the registry record, last updated by the sponsor on 23 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Transcranial Pulse Stimulation (TPS) in Post-COVID-19
- ClinicalTrials.gov ID
- NCT06178952
- Acronym / sponsor ID
- 102307161
- Conditions
- Post-COVID-19 Syndrome, Fatigue
- Keywords
- Transcranial Pulse Stimulation, Post-COVID-19, Fatigue, Non-invasive brain stimulation
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 102 participants (estimated)
- Lead sponsor
- Medical University of ViennaUniversity, hospital or other
- Study start
- 8 Jan 2024 (actual)
- Primary completion
- Jan 2027 (estimated)
- Study completion
- Jan 2027 (estimated)
- First posted
- 21 Dec 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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:
- Initial information session and clarification of relevant medical findings regarding inclusion and exclusion criteria
- 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
- Transcranial pulse stimulation
- 5 stimulations per patient within 10 days
- One stimulation per day lasting approximately 30 minutes.
- Post-stimulation assessment (PostStim)
- Conducted during the week following brain stimulation
- 2-3 assessment sessions per patient within 7 days
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Prospective, double-blind, randomized, parallel group, placebo-controlled trial
| Arm | Type | Receives |
|---|---|---|
| Verum TPS | Experimental | Device: Transcranial pulse stimulation VerumParticipants will receive 5 Verum TPS sessions over a period of 10 days, with a singular daily session, each lasting approximately 30 minutes |
| Sham TPS | Sham comparator | Device: Transcranial pulse stimulation ShamParticipants will receive 5 Sham TPS sessions over a period of 10 days, with a singular daily session, each lasting approximately 30 minutes |
Who may qualify
- Ages
- 20 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Transcranial pulse stimulation VerumParticipants 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. | Device | Verum TPS |
| Transcranial pulse stimulation ShamPlacebo 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. | Device | Sham TPS |
Primary outcome
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.
14 secondary outcomes
Beck Depression Inventory (BDI-II)
Time frame: Baseline - 1 week after stimulation - 1 month after stimulation
Montreal Cognitive Assessment (MOCA)
Time frame: 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
Trail Making Test A and B (TMT-A and TMT-B)
Time frame: 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
Beck Anxiety Inventory (BAI)
Time frame: 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
Test of Attentional Performance (TAP)
Time frame: 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
Stroop color word test (STROOP)
Time frame: 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
Somatization subscale of the Symptom Check List-90-R (SCL-90-R SOM)
Time frame: 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
Neuroimaging
Time frame: Baseline - 1 week after stimulation - 1 month after stimulation
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Dec 2025.
- Background: PubMed 32042569Beisteiner R, Matt E, Fan C, Baldysiak H, Schonfeld M, Philippi Novak T, Amini A, Aslan T, Reinecke R, Lehrner J, Weber A, Reime U, Goldenstedt C, Marlinghaus E, Hallett M, Lohse-Busch H. Transcranial Pulse Stimulation with Ultrasound in Alzheimer's Disease-A New Navigated Focal Brain Therapy. Adv Sci (Weinh). 2019 Dec 23;7(3):1902583. doi: 10.1002/advs.201902583. eCollection 2020 Feb.
- Background: PubMed 36961104Beisteiner R, Hallett M, Lozano AM. Ultrasound Neuromodulation as a New Brain Therapy. Adv Sci (Weinh). 2023 May;10(14):e2205634. doi: 10.1002/advs.202205634. Epub 2023 Mar 24.
- Background: PubMed 36188380Cont C, Stute N, Galli A, Schulte C, Logmin K, Trenado C, Wojtecki L. Retrospective real-world pilot data on transcranial pulse stimulation in mild to severe Alzheimer's patients. Front Neurol. 2022 Sep 14;13:948204. doi: 10.3389/fneur.2022.948204. eCollection 2022.
- Background: PubMed 35255491Douaud G, Lee S, Alfaro-Almagro F, Arthofer C, Wang C, McCarthy P, Lange F, Andersson JLR, Griffanti L, Duff E, Jbabdi S, Taschler B, Keating P, Winkler AM, Collins R, Matthews PM, Allen N, Miller KL, Nichols TE, Smith SM. SARS-CoV-2 is associated with changes in brain structure in UK Biobank. Nature. 2022 Apr;604(7907):697-707. doi: 10.1038/s41586-022-04569-5. Epub 2022 Mar 7.
- Background: PubMed 36642173Ashraf N, Abou Shaar B, Taha RM, Arabi TZ, Sabbah BN, Alkodaymi MS, Omrani OA, Makhzoum T, Almahfoudh NE, Al-Hammad QA, Hejazi W, Obeidat Y, Osman N, Al-Kattan KM, Berbari EF, Tleyjeh IM. A systematic review of trials currently investigating therapeutic modalities for post-acute COVID-19 syndrome and registered on WHO International Clinical Trials Platform. Clin Microbiol Infect. 2023 May;29(5):570-577. doi: 10.1016/j.cmi.2023.01.007. Epub 2023 Jan 13.
- Background: PubMed 35215212Han Q, Zheng B, Daines L, Sheikh A. Long-Term Sequelae of COVID-19: A Systematic Review and Meta-Analysis of One-Year Follow-Up Studies on Post-COVID Symptoms. Pathogens. 2022 Feb 19;11(2):269. doi: 10.3390/pathogens11020269.
- Background: PubMed 36385449Kubota T, Kuroda N, Sone D. Neuropsychiatric aspects of long COVID: A comprehensive review. Psychiatry Clin Neurosci. 2023 Feb;77(2):84-93. doi: 10.1111/pcn.13508. Epub 2022 Dec 12.
- Background: PubMed 36700201Linnhoff S, Koehler L, Haghikia A, Zaehle T. The therapeutic potential of non-invasive brain stimulation for the treatment of Long-COVID-related cognitive fatigue. Front Immunol. 2023 Jan 9;13:935614. doi: 10.3389/fimmu.2022.935614. eCollection 2022.
- Background: PubMed 35033118Matt E, Kaindl L, Tenk S, Egger A, Kolarova T, Karahasanovic N, Amini A, Arslan A, Saricicek K, Weber A, Beisteiner R. First evidence of long-term effects of transcranial pulse stimulation (TPS) on the human brain. J Transl Med. 2022 Jan 15;20(1):26. doi: 10.1186/s12967-021-03222-5.
- Background: PubMed 35169611Matt E, Dorl G, Beisteiner R. Transcranial pulse stimulation (TPS) improves depression in AD patients on state-of-the-art treatment. Alzheimers Dement (N Y). 2022 Feb 10;8(1):e12245. doi: 10.1002/trc2.12245. eCollection 2022.
- Background: PubMed 33144403O'Sullivan O. Long-term sequelae following previous coronavirus epidemics. Clin Med (Lond). 2021 Jan;21(1):e68-e70. doi: 10.7861/clinmed.2020-0204. Epub 2020 Nov 3.
- Background: PubMed 35785594Pinzon RT, Wijaya VO, Jody AA, Nunsio PN, Buana RB. Persistent neurological manifestations in long COVID-19 syndrome: A systematic review and meta-analysis. J Infect Public Health. 2022 Aug;15(8):856-869. doi: 10.1016/j.jiph.2022.06.013. Epub 2022 Jun 23.
- Individual participant dataSharing planned: No. Due to the sensitive nature of the medical information used in the study, access to individual data will not be provided to other researchers.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Roland Beisteiner, Prof. principal investigator
Medical University of Vienna
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Transcranial pulse stimulation Verum in people with Post-COVID-19 Syndrome and Fatigue, run by Medical University of Vienna at 1 site in Austria.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 23 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Austria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Roland Beisteiner, Prof. (+43/(0)1 40400-34080, roland.beisteiner@meduniwien.ac.at), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Fatigue Impact Scale (FIS) (time frame: Baseline - 1 week after stimulation - 1 month after stimulation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06178952, which also lists 19 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Dec 2025.