Clinical trial NCT06178952: Transcranial Pulse Stimulation (TPS) in Post-COVID-19
Official title: Transcranial Pulse Stimulation (TPS) in Post-COVID-19
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Post-COVID-19 Syndrome
Fatigue
Keywords: Transcranial Pulse Stimulation
Post-COVID-19
Fatigue
Non-invasive brain stimulation
Lead sponsor: Medical University of Vienna
Sponsor class: OTHER
Collaborators: name: Campus Bio-Medico University
First posted: 2023-12-21
Enrollment: 120
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective, \[multicenter\], double-blind, randomized, parallel group, placebo-controlled trial
Primary purpose: TREATMENT

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.

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, SF-36 and BI-PEM) 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.

Eligibility criteria: Inclusion Criteria:

* Signed written informed consent
* PCR-confirmed SARS-CoV-2 infection or laboratory confirmed antibody detection for SARS-CoV-2
* 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
* Tumor of the head if relevant for treatment
* Blood clotting disorders
* Participation in other studies

Primary outcomes:
measure: Fatigue Impact Scale (FIS)
timeFrame: Baseline - 1 week after stimulation - 1 month after stimulation
Secondary outcomes:
measure: Beck Depression Inventory (BDI-II)
timeFrame: Baseline - 1 week after stimulation - 1 month after stimulation
measure: Montreal Cognitive Assessment (MOCA)
timeFrame: Baseline - 1 week after stimulation - 1 month after stimulation
measure: 36-Item Short Form Health Survey (SF-36)
timeFrame: Baseline - 1 week after stimulation - 1 month after stimulation
measure: Trail Making Test A and B (TMT-A and TMT-B)
timeFrame: Baseline - 1 week after stimulation - 1 month after stimulation
measure: Positive and Negative Affect Schedule (PANAS)
timeFrame: Baseline - 1 week after stimulation - 1 month after stimulation
measure: Beck Anxiety Inventory (BAI)
timeFrame: Baseline - 1 week after stimulation - 1 month after stimulation
measure: Six Minute Walking Test (6MWT)
timeFrame: Baseline - 1 week after stimulation - 1 month after stimulation
measure: Test of Attentional Performance (TAP)
timeFrame: Baseline - 1 week after stimulation - 1 month after stimulation
measure: Verbal Learning and Memory Test (VLMT)
timeFrame: Baseline - 1 week after stimulation - 1 month after stimulation
measure: Stroop color word test (STROOP)
timeFrame: Baseline - 1 week after stimulation - 1 month after stimulation
measure: Satisfaction With Life Scale (SWLS)
timeFrame: Baseline - 1 week after stimulation - 1 month after stimulation
measure: Somatization subscale of the Symptom Check List-90-R (SCL-90-R SOM)
timeFrame: Baseline - 1 week after stimulation - 1 month after stimulation
measure: Post-Exertional Malaise (BI-PEM)
timeFrame: Baseline - 1 week after stimulation - 1 month after stimulation
measure: Neuroimaging
timeFrame: Baseline - 1 week after stimulation - 1 month after stimulation
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Medical University of Vienna
city: Rome
country: Italy
facility: Università Campus Bio-Medico di Roma
Study officials:
affiliation: Medical University of Vienna
name: Roland Beisteiner, Prof.
role: PRINCIPAL_INVESTIGATOR
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