NCT03681769

Developing Brain Stimulation as a Treatment for Chronic Pain in Opiate Dependent

Completed EARLY_PHASE1 Results posted Last updated 10 February 2023

What this trial tests

EARLY_PHASE1 trial testing iTBS to the left dlPFC in Chronic Pain in 24 participants. Completed in 19 March 2021.

Timeline

22 February 2019

Primary endpoint
19 March 2021

19 March 2021

Quick facts

Lead sponsor	Medical University of South Carolina
Phase	EARLY_PHASE1
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	24
Start date	22 February 2019
Primary completion	19 March 2021
Estimated completion	19 March 2021
Sites	1 location across United States

Drugs / interventions tested

• iTBS to the left dlPFC
• Sham iTBS to the left dlPFC
• cTBS to the mPFC
• Sham cTBS to the mPFC

Conditions studied

• Chronic Pain — all drugs for Chronic Pain →
• Opiate Dependence — all drugs for Opiate Dependence →
• Lower Back Pain — all drugs for Lower Back Pain →

Sponsor

Medical University of South Carolina

Who can join

Adults 18 to 75, any sex, with Chronic Pain or Opiate Dependence. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change in Quantitative Pain Testing Following Active TMS Compared to Baseline Primary · Change from baseline to 16 weeks

Based on pilot data, the investigators expect an interaction between treatment (DLPFC or MC rTMS) and time (Before vs. After rTMS) on reported painfulness using a quantitative sensory testing technique that determines thermal pain threshold.

Group	Value	95% CI
Intermittent Theta Burst Stimulation (iTBS) to the Left dlPFC	1.4	± .3
Intermittent Theta Burst Stimulation (iTBS) to the Motor Cortex	.3	± .15

Change in Patient Reported Pain and Discomfort Secondary · Patient reported pain/discomfort at 16 weeks.

The investigators expect reductions in self reported pain assessment via a numeric pain rating scale when comparing active vs sham. Pain rating values will be assessed and reported through the duration of the study. Numeric Rating Scale (NRS) for pain has a range of 0 to 10 where 0=no pain/discomfort and 10=worst pain/discomfort imaginable. Higher scores mean more pain/discomfort.

Group	Value	95% CI
Intermittent Theta Burst Stimulation (iTBS) to the Left dlPFC	5.3	± 2.4
Intermittent Theta Burst Stimulation (iTBS) to the Motor Cortex	5.9	± 2.0

Sponsor's own description

Effective control of chronic pain is a top priority in the United States, as approximately 10% of adults have severe chronic pain - most of which is chronic lower back pain (CLBP). However, despite the advances in neuroscience over the past 20 years, chronic pain is still largely treated with opiate narcotics, much as was done in the Civil War. In addition to the high abuse liability and dependence potential, only 30-40% of chronic pain patients declare they receive satisfactory (\>50%) relief from their pain through pharmacological treatment. In these patients a common clinical practice is to escalate the dose of opiates as tolerance develops - which unfortunately has contributed to escalation in opiate overdose deaths, a resurgence of intravenous heroin use, and $55 billion in societal costs. Consequently there is a critical need for new, treatments that can treat pain and reduce reliance on opiates in individuals with chronic pain.

Aim 1. Evaluate repetitive Transcranial Magnetic Stimulation (rTMS) to the dorsolateral prefrontal cortex (DLPFC) as a tool to dampen pain and the engagement of the Pain Network. Hypothesis 1: DLPFC TMS will attenuate the baseline brain response to pain (Pain Network activity) and increase activity in the Executive Control Network (ECN) when the patient is given instructions to 'control' the pain.

Aim 2. Evaluate Medial Prefrontal Cortex (MPFC) rTMS as a tool to dampen pain and the engagement of the Pain Network. Hypothesis 1: MPFC TMS will also attenuate the baseline brain response to pain (Pain Network activity) but will not effect the ECN or the Salience Network (SN) when the patient is given instructions to 'control' the pain.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. ACNP 58^th Annual Meeting: Panels, Mini-Panels and Study Groups.
   · 2019 · cited 2× · PMID 31801977 · DOI 10.1038/s41386-019-0544-z