Neuroinflammation in Chronic Systemic Symptoms (CSS)

Completed

• Conditions: Cancer; Neuroinflammatory Response; Chronic Inflammation; Chronic Disease; Chronic Pain; Cancer Head Neck

• Registration Number: NCT04636723
• Lead Sponsor: Vanderbilt University Medical Center

Brief Summary

The purpose of the present research protocol is to investigate and identify translocator protein 18kDa, MRI DTI, and EEG/ERPs, markers of Chronic Systemic Symptoms (CSS).

Detailed Description

In 2016, there were an estimated 15.5 million cancer survivors in the US, with a forecasted 20.3 million by 2026. Three percent of those survivors were treated for Head and neck cancers (HNC). This number is expected to rise due to increased long-term survival in patients with HPV associated oropharyngeal cancer. Increasing survivorship has generated a surge of interest in late effects of HNC therapy. Studies to date have largely focused on chronic effects stemming from local tissue damage. Recent data suggests that late systemic effects may be equally problematic. Chronic systemic symptoms (CSS) persist far longer than previously considered and are the source of significant function loss and detriment to quality of life. CSS include fatigue, neurocognitive dysfunction, centralized pain, mood disorders, sleep disturbances, and hypothalamic dysfunction manifested as thermal discomfort or hyperhidrosis. Systemic symptoms occur in clusters resulting in a heightened clinical impact. As with other critical illnesses, the trajectory of recovery from the systemic symptoms from cancer treatment is varied. Some patients will recover to baseline quickly post treatment while others display CSS that persist or worsen over time resulting in functional deficits, frailty, and an early aging phenotype which may impact survival. Survivors exhibiting a "slow burn" trajectory as manifested by persistent systemic symptom burden and worsening function over time, require extensive on-going long-term management. These patients often fail to return to work or previously held family roles. CSS may therefore be associated with greater economic cost than the initial treatment.

Work that spans a wide array of inflammatory disease processes (such as fibromyalgia, chronic fatigue syndrome, irritable bowel, etc.) demonstrate the presence of somatic, affective, and cognitive symptoms. Neuroinflammation is hypothesized to be the underlying cause of these symptoms and their manifestations. More specifically, peripheral injury/trauma/cancer release inflammatory mediators that activate glial components of peripheral and central cellular circuitry causing inflammation of the CNS. However, the concept that CSS is underlined by neuroinflammation is largely theoretical from disparate and indirect evidence. A gap in the evidence base suggests direct investigation of neuroinflammation in CSS patients in capturing a mechanistic marker is urgently needed in order to (1) present CSS as a diagnostic entity, (2) fully understand its neurobiological mechanism, and (3) test/develop appropriate treatments.

Study Timeline

• Study First Submitted: 2020-11-13
• Study First Submitted QC: 2020-11-13
• Study First Posted: 2020-11-19
• Study Start: 2021-02-22
• Primary Completion: 2021-12-07
• Study Completion: 2021-12-07
• Status Verified: 2023-01
• Last Update Submitted: 2023-01-23
• Last Update Posted: 2023-01-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Positron Emission Tomography (PET)	12 months	Centralized Microglial Activation measured via mitochondrial translocator protein 18kDa (TSPO).

Secondary Outcome Measures

Name	Time	Method
EEG/ERP concomitant to working memory neurobehavioral task	12 months	Cognitive function as recommended by the International Cognition and Cancer Task Force (ICCTF)
EEG/ERP concomitant to sustained attention neurobehavioral task	12 months	Cognitive function as recommended by the International Cognition and Cancer Task Force (ICCTF)
Diffusion Tensor Imaging (DTI)	12 months	Diffusion coefficients as measure of cellular inflammation
Peripheral Cytokine and Chemokine Inflammation	12 months	Blood marker nuclear factor (NF)-kB transcription factor

Trial Locations

Locations (1)

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States