CancerNCT04636723
Neuroinflammation in Chronic Systemic Symptoms (CSS)
An observational study of Cancer and Cancer Head Neck, run by Vanderbilt University Medical Center at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 21 years and olderHealthy volunteers can take part
- Conditions the study is for
- Cancer, Cancer Head Neck, Neuroinflammatory Response
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Feb 2021to 7 Dec 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
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.
Who may be able to join
- 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
- Age ≥ 21
- Able to speak English to understand instructions and be able to provide informed consent
Who cannot join
- 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.
- History of HNC of larynx, pharynx, oral cavity paranasal sinus, salivary gland, or unknown primary
Show all 10Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Vanderbilt University Medical Center
Nashville, Tennessee, 37203
About this study
Official title: Neuroinflammation in Chronic Systemic Symptoms (CSS): Proof-of-Concept Study Using PET and EEG/ERP Biomarkers
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).
Read the 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.
- Conditions
- Cancer, Cancer Head Neck, Neuroinflammatory Response, Chronic Inflammation, Chronic Disease, Chronic Pain
- Keywords
- PET, EEG/ERP, MRI/DTI, Cytokine, Chemokine, Neurophysiology, Molecular Radiology
- Medical subject headings
- Neoplasms, Head and Neck Neoplasms, Chronic Disease, Chronic Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| HNC Patients w/ CSS | HNC survivor patients presenting high chronic systemic symptoms | |
| Healthy Controls | Non-clinical controls | |
| HNC Patients wo/ CSS | Patient Control - HNC survivor patients presenting no/low chronic systemic symptoms |
What is being measured
The primary outcome is the main question the study is designed to answer.
Positron Emission Tomography (PET)
Centralized Microglial Activation measured via mitochondrial translocator protein 18kDa (TSPO).
Measured: 12 months
Secondary outcomes (6)
EEG/ERP concomitant to working memory neurobehavioral task
Cognitive function as recommended by the International Cognition and Cancer Task Force (ICCTF)
Measured: 12 months
EEG/ERP concomitant to sustained attention neurobehavioral task
Cognitive function as recommended by the International Cognition and Cancer Task Force (ICCTF)
Measured: 12 months
Diffusion Tensor Imaging (DTI)
Diffusion coefficients as measure of cellular inflammation
Measured: 12 months
Peripheral Cytokine and Chemokine Inflammation
Blood marker Interleukin-6 (IL-6)
Measured: 12 months
Peripheral Cytokine and Chemokine Inflammation
Blood marker C reactive protein (CRP)
Measured: 12 months
Peripheral Cytokine and Chemokine Inflammation
Blood marker nuclear factor (NF)-kB transcription factor
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2020
- Study start22 Feb 2021
- Primary completion7 Dec 2021
- Study completion7 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CancerStudies of the same condition, open and under way.
- More trials run by Vanderbilt University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Vanderbilt-Ingram Cancer Center
- Responsible party
- Principal investigator, Poppy Schoenberg, Vanderbilt University Medical Center
- Investigators
- Poppy Schoenberg, PhD, Principal investigator, Osher Center for Integrative Medicine, VANDERBILT UNIVERSITY MEDICAL CENTER
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04636723
- Sponsor's protocol ID
- IRB #202009
- Status last verified
- Jan 2023
- First submitted
- 13 Nov 2020
- Last updated
- 26 Jan 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The PI will adhere to the NIH Sharing of Biomedical Research Resources: Guidelines for Recipients of NIH Grants and Contracts on Obtaining and Disseminating Biomedical Research Resources. 1. Quality-controlled raw data as well as processed data used in publications will be de-identified before sharing upon "reasonable request". As described in the proposal, workflows and structure will be exactly described in reports and documented to allow precisely reproduce results from raw data and replicate methodology. Final data (computerized datasets with raw data and derived variables) that have not yet been published will be shared in a timely manner. 2. Software programs (i.e. experimental paradigm scripts produced for this study) and documentation will be made available for research purposes to replicate findings upon "reasonable request", and any software/script sharing requirements by journals.
Study at a glance
From the registry record, last updated by the sponsor on 26 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neuroinflammation in Chronic Systemic Symptoms (CSS): Proof-of-Concept Study Using PET and EEG/ERP Biomarkers
- ClinicalTrials.gov ID
- NCT04636723
- Acronym / sponsor ID
- IRB #202009
- Conditions
- Cancer, Cancer Head Neck, Neuroinflammatory Response, Chronic Inflammation, Chronic Disease, Chronic Pain
- Keywords
- PET, EEG/ERP, MRI/DTI, Cytokine, Chemokine, Neurophysiology, Molecular Radiology
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Vanderbilt University Medical CenterUniversity, hospital or other
- Collaborators
- Vanderbilt-Ingram Cancer Center
- Study start
- 22 Feb 2021 (actual)
- Primary completion
- 7 Dec 2021 (actual)
- Study completion
- 7 Dec 2021 (actual)
- First posted
- 19 Nov 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| HNC Patients w/ CSS | – | –HNC survivor patients presenting high chronic systemic symptoms |
| Healthy Controls | – | –Non-clinical controls |
| HNC Patients wo/ CSS | – | –Patient Control - HNC survivor patients presenting no/low chronic systemic symptoms |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (8 listed)
Key exclusion criteria (10 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Positron Emission Tomography (PET)
Time frame: 12 months
Centralized Microglial Activation measured via mitochondrial translocator protein 18kDa (TSPO).
6 secondary outcomes
EEG/ERP concomitant to working memory neurobehavioral task
Time frame: 12 months
EEG/ERP concomitant to sustained attention neurobehavioral task
Time frame: 12 months
Diffusion Tensor Imaging (DTI)
Time frame: 12 months
Peripheral Cytokine and Chemokine Inflammation
Time frame: 12 months
Peripheral Cytokine and Chemokine Inflammation
Time frame: 12 months
Peripheral Cytokine and Chemokine Inflammation
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jan 2023.
- Individual participant dataSharing planned: Yes. The PI will adhere to the NIH Sharing of Biomedical Research Resources: Guidelines for Recipients of NIH Grants and Contracts on Obtaining and Disseminating Biomedical Research Resources. 1. Quality-controlled raw data as well as processed data used in publications will be de-identified before sharing upon "reasonable request". As described in the proposal, workflows and structure will be exactly described in reports and documented to allow precisely reproduce results from raw data and replicate methodology. Final data (computerized datasets with raw data and derived variables) that have not yet been published will be shared in a timely manner. 2. Software programs (i.e. experimental paradigm scripts produced for this study) and documentation will be made available for research purposes to replicate findings upon "reasonable request", and any software/script sharing requirements by journals.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Poppy Schoenberg, PhD principal investigator
Osher Center for Integrative Medicine, VANDERBILT UNIVERSITY MEDICAL CENTER
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cancer and Cancer Head Neck, run by Vanderbilt University Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Positron Emission Tomography (PET) (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Jan 2023.