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

NCT06178952 | Recruiting FDA Device

• 1 other identifier: 102307161
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 1

Brief 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. The verum treatment will be compared to a sham (placebo) condition.

Conditions

Fatigue; Post-COVID-19 Syndrome

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline - 1 week after stimulation - 1 month after stimulation

Secondary Outcomes (14)

• Beck Depression Inventory (BDI-II)

  Baseline - 1 week after stimulation - 1 month after stimulation

• Montreal Cognitive Assessment (MOCA)

  Baseline - 1 week after stimulation - 1 month after stimulation

• 36-Item Short Form Health Survey (SF-36)

  Baseline - 1 week after stimulation - 1 month after stimulation

• Trail Making Test A and B (TMT-A and TMT-B)

  Baseline - 1 week after stimulation - 1 month after stimulation

• Positive and Negative Affect Schedule (PANAS)

  Baseline - 1 week after stimulation - 1 month after stimulation

Study Arms (2)

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

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

Device: Transcranial pulse stimulation Sham

Interventions

Transcranial pulse stimulation Verum 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.

Verum TPS

Transcranial pulse stimulation Sham 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.

Sham TPS

Eligibility Criteria

• Age: 20 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed written informed consent
• PCR-confirmed SARS-CoV-2 infection, laboratory confirmed antibody detection for SARS-CoV-2, or physician-verified COVID-19 infection
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Medical University of Vienna: lead

Study Sites (1)

Medical University of Vienna

Vienna, Vienna, 1090, Austria

RECRUITING

Related Publications (19)

• 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.

  PMID: 32042569 BACKGROUND

• Beisteiner 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.

  PMID: 36961104 BACKGROUND

• Cont 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.

  PMID: 36188380 BACKGROUND

• Douaud 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.

  PMID: 35255491 BACKGROUND

• Ashraf 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.

  PMID: 36642173 BACKGROUND

• Han 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.

  PMID: 35215212 BACKGROUND

• Kubota 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.

  PMID: 36385449 BACKGROUND

• Linnhoff 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.

  PMID: 36700201 BACKGROUND

• Matt 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.

  PMID: 35033118 BACKGROUND

• Matt 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.

  PMID: 35169611 BACKGROUND

• O'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.

  PMID: 33144403 BACKGROUND

• Pinzon 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.

  PMID: 35785594 BACKGROUND

• Popescu 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.

  PMID: 33681449 BACKGROUND

• Radjenovic S, Dorl G, Gaal M, Beisteiner R. Safety of Clinical Ultrasound Neuromodulation. Brain Sci. 2022 Sep 22;12(10):1277. doi: 10.3390/brainsci12101277.

  PMID: 36291211 BACKGROUND

• Santana 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.

  PMID: 36693536 BACKGROUND

• Soriano JB, Murthy S, Marshall JC, Relan P, Diaz JV; WHO Clinical Case Definition Working Group on Post-COVID-19 Condition. A clinical case definition of post-COVID-19 condition by a Delphi consensus. Lancet Infect Dis. 2022 Apr;22(4):e102-e107. doi: 10.1016/S1473-3099(21)00703-9. Epub 2021 Dec 21.

  PMID: 34951953 BACKGROUND

• Tran VT, Porcher R, Pane I, Ravaud P. Course of post COVID-19 disease symptoms over time in the ComPaRe long COVID prospective e-cohort. Nat Commun. 2022 Apr 5;13(1):1812. doi: 10.1038/s41467-022-29513-z.

  PMID: 35383197 BACKGROUND

• Weinreb E, Moses E. Mechanistic insights into ultrasonic neurostimulation of disconnected neurons using single short pulses. Brain Stimul. 2022 May-Jun;15(3):769-779. doi: 10.1016/j.brs.2022.05.004. Epub 2022 May 11.

  PMID: 35561960 BACKGROUND

• Zeng N, Zhao YM, Yan W, Li C, Lu QD, Liu L, Ni SY, Mei H, Yuan K, Shi L, Li P, Fan TT, Yuan JL, Vitiello MV, Kosten T, Kondratiuk AL, Sun HQ, Tang XD, Liu MY, Lalvani A, Shi J, Bao YP, Lu L. A systematic review and meta-analysis of long term physical and mental sequelae of COVID-19 pandemic: call for research priority and action. Mol Psychiatry. 2023 Jan;28(1):423-433. doi: 10.1038/s41380-022-01614-7. Epub 2022 Jun 6.

  PMID: 35668159 BACKGROUND

MeSH Terms

Conditions

Post-Acute COVID-19 Syndrome; Fatigue

Condition Hierarchy (Ancestors)

COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Post-Infectious Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms

Study Officials

• Roland Beisteiner, Prof.

  Medical University of Vienna

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Roland Beisteiner, Prof.

CONTACT

+43/(0)1 40400-34080; roland.beisteiner@meduniwien.ac.at

Michael Mitterwallner, Dr.

CONTACT

+43 650 9626003; michael.mitterwallner@meduniwien.ac.at

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Prospective, double-blind, randomized, parallel group, placebo-controlled trial

Study Record Dates

• First Submitted: December 20, 2023
• First Posted: December 21, 2023
• Study Start: January 8, 2024
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027
• Last Updated: December 23, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)