PAINLESS: protocol for a triple-blinded randomized sham-controlled multicenter trial of home-based transcranial electrical stimulation for pain management in patients with cancer

TL;DR

This study tests home-based brain stimulation to manage cancer pain, using EEG and sensory tests to understand how it works.

Contribution

The study introduces a novel triple-blinded trial protocol for transcranial electrical stimulation in cancer pain management.

Findings

The trial will assess the efficacy of tDCS and tACS in reducing cancer-related pain.

EEG and QST data will provide insights into the mechanisms of tES-induced analgesia.

Results may identify biomarkers for personalizing tES interventions.

Abstract

Pain is a common debilitating symptom in cancer patients and its management remains a challenge. Among the non-pharmacological analgesic treatment options, low intensity transcranial electrical stimulation (tES) represents a new unique analgesic modality. However, the evidence of tES effectiveness for cancer pain is limited, while the mechanisms of pain relief due to tES are still poorly understood. We propose to test the efficacy of repetitive transcranial direct current stimulation (tDCS) and alternating current stimulation (tACS) in cancer pain patients, and attempt to understand their mechanisms using electroencephalography (EEG) and quantitative sensory testing (QST) measures.

This article describes the protocol of a multicenter, sham-controlled, parallel-arm, triple-blinded randomized clinical trial assessing home-based tDCS and tACS in the treatment of cancer patients with persistent pain. 450 patients between 18 and 75 years old will be enrolled in this study. Treatment consists of 15 consecutive daily sessions of either anodal tDCS at 2 mA targeting the primary motor cortex or 10 Hz tACS targeting the dorsolateral prefrontal cortex. Following randomization (2:2:1 ratio), 180 patients will receive active tDCS, 180 patients active tACS, and 90 patients sham stimulation. The primary outcome is self-reported pain intensity on a numerical rating scale (NRS) assessed daily (15 days pre-treatment, 15 days during treatment and 15 days post-treatment). The secondary endpoints are medication intake, other cancer-associated symptoms and quality of life. We will also analyze psychophysical and neurophysiological correlates of ascending and descending pain processing using QST and EEG paradigms. Besides the NRS, which will be reported daily, assessments will be conducted at baseline (T0) and at three time points post-intervention (T1, T2, and T3).

Positive findings of the study will indicate the therapeutic benefit of tES in patients with cancer-related pain. Group differences in mechanistic measures would yield potential biomarkers for tDCS- and tACS-induced analgesia, which could be used for personalizing and optimizing the intervention. In addition, changes in EEG or QST could provide insights into the mechanisms underlying the tES effects.

The study was registered at the German Clinical Trials Register under the identification number DRKS00031070.

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