Uncovering Neural and Immune Mechanisms of Chronic Pain in Post Treatment Lyme Syndrome — CP-PTLS  

Chronic Pain Clinical Trial

Official title: Uncovering Neural and Immune Mechanisms Underlying Chronic Pain and Central Sensitization in Post-treatment Lyme Syndrome

Status Terminated

Clinical Trial Summary

This study that has the following goals:

a) To systematically characterize symptomatology of patients with PTLS by conducting multimodal sensory and neurocognitive assessments and comparing patients with PTLS to healthy controls and to identify biomarkers associated with chronic pain and sensory hypersensitivity among patients with PTLS, c) To investigate whether pharmacologic treatment with milnacipran is associated with clinical improvement chronic pain and physical functioning and with specific changes both in the cerebral and ventricular neurochemistry and in the neural activation patterns d) To investigate whether augmentation with a glutamatergic agent (D-cycloserine) can increase the pain -alleviating effect of an SNRI agent (milnacipran) among patients with PTLS

First, patients with chronic PTLS pain and healthy controls will carefully assessed and compared on the brain imaging measures, sensory battery, neuropsychologic tests, and immune markers. After this extensive clinical and neural markers assessment, patients with PTLS and chronic pain will be randomized to (i) 12 weeks of milnacipran +d-cycloserine augmentation, or (ii) 12 weeks of milnacipran + placebo augmentation. Milnacipran (an SNRI) reduces both pain and depression and was shown in previos studies to reduce pain in fibromyalgia. D-Cycloserine (as a glutamate modulator) as a SNRI adjunct was shown to further reduce depression and in animal models to reduce pain. Primary outcome measure will be improvement in pain on visual analog scale, physical functioning and quality of life. All patients will undergo sensory, immune, glycine, self-reports, neuropsychologic testing, and neural markers assessments pre- and post-treatment.

Clinical Trial Description

At least 5-15% of patients with Lyme disease (7,500-45,000 new cases a year) develop Post-treatment Lyme Syndrome (PTLS) - debilitating residual symptoms that last months to years despite antibiotic treatment. Many patients with PTLS experience chronic widespread pain which may be mediated by the process of central sensitization. To date, central neural mechanisms underlying this debilitating syndrome are still unknown, and, to our knowledge, there have been no studies exploring the aberrantly working neural pain circuits, neurochemistry, and possible associated immune system dysregulation in PTLS. Understanding the central neural and immune markers of PTLS can lead to the development of new targeted treatments, which are urgently needed.

There are also no known treatments for patients with persistent widespread pain after antibiotic-treatment for Lyme disease. Because SNRIs have been shown to be helpful in reducing pain among patients with central sensitization syndromes (e.g., fibromyalgia), treatment with a SNRI would be expected to help patients with PTLS. However the magnitude of this effect is modest, ranging from mild to moderate in different studies. Agents that augment the improvement in pain are needed. We propose to conduct a study that has the following goals:a) To systematically characterize symptomatology of patients with PTLS by conducting multimodal sensory and neurocognitive assessments and comparing patients with PTLS to healthy controls b) To identify biomarkers associated with chronic pain and sensory hypersensitivity among patients with PTLS, including: immune markers, neural circuits involved in pain processing, and neurochemistry of pain processing brain regions (glutamate and GABA in the insula)c) To investigate whether pharmacologic treatment with milnacipran with/without DCS is associated with clinical improvement and with specific changes both in the cerebral and ventricular neurochemistry and in the neural activation patterns d) To investigate whether augmentation with a glutamatergic agent (D-cycloserine) can increase the pain -alleviating effect of an SNRI agent (milnacipran) among patients with PTLS.

To accomplish this, first, 40 patients with PTLS and chronic pain and 20 healthy controls will carefully assessed and compared on the following measures: Multimodal Sensory Battery (thermal, pressure, vibration, sound, & light sensitivity); neurocognitive testing; self-report measures of pain, fatigue, mood, functioning, quality of life, lifetime stressors, peripheral neuropathy; physical exam and detailed medical history; lab testing for Lyme and co-infections; serum glycine; autonomic nervous system measures; neural circuits in the brain using fMRI during rest and reactivity to pain stimuli; neurochemistry of the brain using MRS, including Glutamate & GABA in pain regions (anterior and posterior insula) as well as ventricular lactate; immune markers (cytokines and chemokines using stimulated macrophage methodology -lipopolysaccharide (LPS) challenge). After this extensive clinical and neural markers assessment, 40 patients with PTLS and chronic pain will be randomized to (i) 12 weeks of milnacipran +d-cycloserine augmentation or (ii) 12 weeks of milnacipran + placebo augmentation. Primary outcome measure will be improvement in pain on visual analog scale, physical functioning and quality of life. Milnacipran (an SNRI) reduces both pain and depression and was shown in previos studies to reduce pain in fibromyalgia. D-Cycloserine (as a glutamate modulator) as a SNRI adjunct was shown to further reduce depression and in animal models to reduce pain.All patients will undergo sensory, immune, glycine, self-reports, neuropsychologic testing, and neural markers assessments pre- and post-treatment. ;

Related Conditions & MeSH terms

• Central Sensitization
• Chronic Pain
• Syndrome

• NCT number: NCT05055622
• Study type: Interventional
• Source: Research Foundation for Mental Hygiene, Inc.
• Status: Terminated
• Phase: Phase 2
• Start date: December 2015
• Completion date: January 27, 2018