Clinical trial NCT04636723: Neuroinflammation in Chronic Systemic Symptoms (CSS)
Official title: Neuroinflammation in Chronic Systemic Symptoms (CSS): Proof-of-Concept Study Using PET and EEG/ERP Biomarkers
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cancer
Cancer Head Neck
Neuroinflammatory Response
Chronic Inflammation
Chronic Disease
Chronic Pain
Keywords: PET
EEG/ERP
MRI/DTI
Cytokine
Chemokine
Neurophysiology
Molecular Radiology
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
Collaborators: name: Vanderbilt-Ingram Cancer Center
First posted: 2020-11-19
Enrollment: 30
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 10x HNC patients will be recruited via Vanderbilt's Department of Otolaryngology.

10x Healthy controls will be recruited via VUMC recruitment listserv and ResearchMatch.

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.

Eligibility criteria: * 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.

Primary outcomes:
measure: Positron Emission Tomography (PET)
timeFrame: 12 months
Secondary outcomes:
measure: EEG/ERP concomitant to working memory neurobehavioral task
timeFrame: 12 months
measure: EEG/ERP concomitant to sustained attention neurobehavioral task
timeFrame: 12 months
measure: Diffusion Tensor Imaging (DTI)
timeFrame: 12 months
measure: Peripheral Cytokine and Chemokine Inflammation
timeFrame: 12 months
measure: Peripheral Cytokine and Chemokine Inflammation
timeFrame: 12 months
measure: Peripheral Cytokine and Chemokine Inflammation
timeFrame: 12 months
Other outcomes:
measure: Clinical Measure: Vanderbilt Head and Neck Symptom Survey (VHNSS) version 2.0 plus general symptom survey (GSS)
timeFrame: 12 months
measure: Clinical Measure: Neurotoxicity Rating Scale (NRS)
timeFrame: 12 months
measure: Clinical Measure: Central Sensitivity Inventory (CSI)
timeFrame: 12 months
measure: Clinical Measure: Pain Inventory (PI)
timeFrame: 12 months
measure: Clinical Measure: Patient Reported Outcomes Measurement Information System (PROMIS-29)
timeFrame: 12 months
measure: Clinical Measure: • Behavior Rating Inventory of Executive Function - Adult version (BRIEF-A)
timeFrame: 12 months
Locations:
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
affiliation: Osher Center for Integrative Medicine, VANDERBILT UNIVERSITY MEDICAL CENTER
name: Poppy Schoenberg, PhD
role: PRINCIPAL_INVESTIGATOR
References: