Neuroinflammation in Chronic Systemic Symptoms (CSS)

Sponsor

Vanderbilt University Medical Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT04636723

Collaborator

Vanderbilt-Ingram Cancer Center (Other)

Enrollment

Location

28.2

Anticipated Duration (Months)

1.1

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Cancer Cancer Head Neck Neuroinflammatory Response Chronic Inflammation Chronic Disease Chronic Pain

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 Design

Study Type:

Observational

Anticipated Enrollment :

30 participants

Observational Model:

Cohort

Time Perspective:

Cross-Sectional

Official Title:

Neuroinflammation in Chronic Systemic Symptoms (CSS): Proof-of-Concept Study Using PET and EEG/ERP Biomarkers

Actual Study Start Date :

Feb 22, 2021

Anticipated Primary Completion Date :

Jun 30, 2022

Anticipated Study Completion Date :

Jun 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
CSS Patients HNC patients presenting chronic systemic symptoms
Healthy Controls Non-clinical controls

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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 Interleukin-6 (IL-6)
Peripheral Cytokine and Chemokine Inflammation [12 months]
Blood marker C reactive protein (CRP)
Peripheral Cytokine and Chemokine Inflammation [12 months]
Blood marker nuclear factor (NF)-kB transcription factor

Other Outcome Measures

Clinical Measure: Vanderbilt Head and Neck Symptom Survey (VHNSS) version 2.0 plus general symptom survey (GSS) [12 months]
Validated tool to measure physical symptom burden and functional deficits related to head/neck cancer and its treatment.
Clinical Measure: Neurotoxicity Rating Scale (NRS) [12 months]
37 item tool examining neurocognitive symptoms associated with neurotoxicity of medical treatment.
Clinical Measure: Central Sensitivity Inventory (CSI) [12 months]
Two-part survey consisting of 35 questions. Part A aims to identify frequency of experienced systemic symptoms. Part B determines previous diagnosis of Central Sensitivity Syndromes or related disorders.
Clinical Measure: Pain Inventory (PI) [12 months]
Diagram in which patients document specific areas of pain in the body, and rate pain intensity on a scale 1-10 in the past 3 months (i.e. with scores 3+ constituting chronic pain).
Clinical Measure: Patient Reported Outcomes Measurement Information System (PROMIS-29) [12 months]
assesses 7 domains (depression, anxiety, physical function, pain interference, fatigue, sleep disturbance, participation in social roles/activities) using 5-point Likert scale, across 29-items.
Clinical Measure: • Behavior Rating Inventory of Executive Function - Adult version (BRIEF-A) [12 months]
Measures nine non-overlapping theoretically and empirically derived clinical domains: Inhibit, Self-Monitor, Plan/Organize, Shift, Initiate, Task Monitor, Emotional Control, Working Memory, and organization of Materials.

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria for HNC patients:
Age ≥ 21
HNC of larynx, pharynx, oral cavity paranasal sinus, salivary gland, or unknown primary
Any histology of any epithelial origin
Completed therapy a minimum of 3 months prior to study entry
At least two systemic symptoms on the VHNSS-GSS subscale
Able to speak English to understand instructions and be able to provide informed consent
Exclusion Criteria for HNC patients:
History of neurodegenerative disease, unrelated to cancer history/treatment
Alcohol/substance abuse/dependence within the last 6 months
Current or previous co-morbid bipolar disorder-, psychosis-, obsessive compulsive disorder-, eating disorders-, personality disorders-,
Neurological disorders unrelated to cancer and its treatment (e.g. ADHD, ASDs, epilepsy)
Learning difficulties.
Inclusion Criteria for healthy controls:
Age ≥ 21
Able to speak English to understand instructions and be able to provide informed consent
Exclusion Criteria for healthy controls:
History of HNC of larynx, pharynx, oral cavity paranasal sinus, salivary gland, or unknown primary
Alcohol/substance abuse/dependence within the last 6 months
Current or previous co-morbid bipolar disorder-, psychosis-, obsessive compulsive disorder-, eating disorders-, personality disorders-,
Neurological disorders (e.g. ADHD, ASDs, epilepsy)
Learning difficulties.