Transcutaneous Auricular Vagal Nerve Stimulation for the Treatment of the Fatigue Syndrome in Patients with Primary CNS Lymphoma - A Protocol for a Randomized and Controlled Single Center Clinical Trial.

in Advances in therapy by Mortimer Gierthmuehlen, Sabine Seidel, Niklas Thon, Corinna Seliger

TLDR

  • This randomized controlled trial (RCT) investigates the effect of transcutaneous auricular vagal nerve stimulation (taVNS) on fatigue symptoms in patients with primary central nervous lymphoma (PCNSL).
  • Forty-five adult patients with PCNSL and fatigue will be recruited and randomized into three groups: active stimulation, sub-threshold stimulation, and sham group.
  • The primary outcome measure is the Multidimensional Fatigue Inventory (MFI20) questionnaire, which will be collected at the beginning and end of the 8-week study.

Abstract

Cancer-Related Fatigue (CRF) is characterized as a distressing, persistent, and subjective sensation of physical, emotional, and/or cognitive exhaustion that is associated with cancer or its treatment. CRF is commonly observed in patients with cancer and a severely impairing symptom also in patients with the rare primary central nervous lymphoma (PCNSL). While its exact etiology remains unclear, elevated levels of tumor-induced inflammatory cytokines are believed to contribute to its development. Transcutaneous auricular vagal nerve stimulation (taVNS) is a non-invasive method to activate the vagal nerve through electrical stimulation of a vagally innervated area at the tragus. It has shown to modulate the immunsystem, to activate central arousal pathways and to reduce fatigue in autoimmune conditions. In this study, the effect of taVNS on the fatigue syndrome in patients with PCNSL will be investigated. For this single-blinded, sham controlled, randomized controlled trial (RCT), 45 adult patients with PCNSL and fatigue in Multidimensional Fatigue Inventory (MFI20)-questionnaire after active treatment will be recruited and randomized to above-threshold-stimulation (A) sub-threshold-stimulation (B) or sham group (C). In Arm A, taVNS is perfomed on the left tragus (25 Hz, pulse width 250 µs,28 s on/32 s off,4 h/day). In Arm B, the patients will be asked to regulate the stimulator below perception threshold. In Arm C, the patients are initially shown how stimulation feels and then asked to decrease the intensity below perception threshold. They then take a non-functional sham-electrode home. Validated questionnaires data (MFI20, Beck Depression Inventory (BDI2), Short-form 26 (SF36), NeuroCogFx and Neurologic Assessment in Neuro-Oncology (NANO) and Hospital Anxiety Depression Scale (HADS)) will be collected at the beginning of the study and after 4 and 8 weeks. This is the first clinical trial to assess if taVNS improves fatigue symptoms in patients with the primary CNS lymphoma. If taVNS improves fatigue in these patients, it will be a significant gain in quality of life. The study was approved by the ethics committee (2024-368-f-S) and registered at the DRKS database (DRKS00036323).

Overview

  • The study investigates the effect of transcutaneous auricular vagal nerve stimulation (taVNS) on fatigue symptoms in patients with primary central nervous lymphoma (PCNSL).
  • Forty-five adult patients with PCNSL and fatigue will be recruited and randomized into three groups: active stimulation, sub-threshold stimulation, and sham group.
  • The primary objective is to assess if taVNS improves fatigue symptoms in patients with PCNSL, which could result in a significant gain in quality of life.

Comparative Analysis & Findings

  • The study is a single-blinded, sham-controlled, randomized controlled trial (RCT) with three groups: active stimulation, sub-threshold stimulation, and sham group.
  • The primary outcome measure is the Multidimensional Fatigue Inventory (MFI20) questionnaire, which will be collected at the beginning of the study and after 4 and 8 weeks.
  • The study will also assess additional outcomes, including depression, anxiety, cognitive function, and quality of life using validated questionnaires.

Implications and Future Directions

  • If taVNS is found to improve fatigue symptoms in patients with PCNSL, it could be a significant gain in quality of life, offering a non-invasive and potentially effective treatment option.
  • Future studies could explore the mechanism of action of taVNS in reducing fatigue and its potential application in other patient populations.
  • The results of this study could also inform the development of new treatments for cancer-related fatigue and improve the overall management of patients with PCNSL.
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