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This study is examining the effects of standard of care cancer treatment as well as a medication called Sildenafil, on the cancer associated fatigue, cognition and the gut microbiome.
Cancer related cognitive impairment (CRCI) severely impacts neurocognitive function and is characterized by deficits in memory, learning, processing speed, and executive function. This cognitive impairment commonly referred to as "brain fog" or "chemo-brain," often co-occurs with central and peripheral fatigue. Symptoms typically begin acutely with the initiation of therapy, and persist chronically throughout prolonged treatment. Despite advancements in cytotoxic chemotherapies, CRCI plagues 75% of breast cancer patients during treatment, and development of new therapeutic options have been hampered by an incomplete understanding of the underlying mechanisms that cause CRCI. Although the etiology is not clear, CRCI is known to be associated with oxidative stress, increased inflammation, and disruption to the blood-brain barrier (BBB). Importantly, the endothelial cells of the BBB protect the central nervous system (CNS) from harmful and inflammatory bloodborne factors. Similarly, endothelial and epithelial barriers in the gut prevent microbial invasion and resulting regional and systemic inflammatory signaling. Thus, gut and brain barriers regulate exposure of the CNS to inflammatory factors and represent an important source of communication in the gut-brain axis. Research suggests that cytotoxic chemotherapeutic agents compromise both brain and gut endothelial and epithelial barrier integrity, leading to extravasation of toxins and immune cells into the CNS, causing neuroinflammation and CRCI. This study proposes that sildenafil, a phosphodiesterase-5 (PDE-5) inhibitor, will preserve barrier integrity during chemotherapy by downregulating oxidative and nitrosative stress that leads to endothelial dysfunction via multiple pathways. Thus, the goal of this project is to interrogate how chemotherapy-induced brain and gut barrier dysfunction mediate CRCI, neurotoxicity, and neuro- and systemic inflammation. Outcomes will be measured at baseline and throughout standard of care treatment, specifically after neoadjuvant chemotherapy, surgery, radiation treatment, chemotherapy treatment and after 24 weeks of endocrine treatment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Standard of Care Treatment | No Intervention | standard of care treatment | |
| Standard of Care Treatment and Sildenafil | Experimental | Sildenafil, 50mg, daily for duration of the standard of care treatment |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sildenafil | Drug | Sildenafil, 50mg, daily |
|
| Measure | Description | Time Frame |
|---|---|---|
| Fatigue and Cognition as measured by the Fatigue and Altered Cognition Scale at baseline | The Fatigue and Altered Cognition Scale (FACS) is a joint project from University of Texas Medical Branch and Texas A&M University. The FACS is a 20 question assessment designed to access perceived fatigue and cognition. There are 2 subscales used to calculate a total score. The subscales are: Fatigue and Altered Cognition. The total score is calculated by adding the subscales together. The range of the total score is 0-100, with a higher score indicating more fatigue and altered cognition. | Baseline |
| Fatigue and Cognition as measured by the Fatigue and Altered Cognition Scale after neoadjuvant chemotherapy treatment | The Fatigue and Altered Cognition Scale (FACS) is a joint project from University of Texas Medical Branch and Texas A&M University. The FACS is a 20 question assessment designed to access perceived fatigue and cognition. There are 2 subscales used to calculate a total score. The subscales are: Fatigue and Altered Cognition. The total score is calculated by adding the subscales together. The range of the total score is 0-100, with a higher score indicating more fatigue and altered cognition. | through neoadjuvant chemotherapy treatment completion, average of 20 weeks from baseline |
| Fatigue and Cognition as measured by the Fatigue and Altered Cognition Scale after surgery | The Fatigue and Altered Cognition Scale (FACS) is a joint project from University of Texas Medical Branch and Texas A&M University. The FACS is a 20 question assessment designed to access perceived fatigue and cognition. There are 2 subscales used to calculate a total score. The subscales are: Fatigue and Altered Cognition. The total score is calculated by adding the subscales together. The range of the total score is 0-100, with a higher score indicating more fatigue and altered cognition. | through completion of surgery, average of 24 weeks from baseline |
| Fatigue and Cognition as measured by the Fatigue and Altered Cognition Scale after radiation treatment |
| Measure | Description | Time Frame |
|---|---|---|
| Quantify absolute abundance of gut microbiome using using metagenomic analysis at baseline | Metagenomic analysis using a custom PCR array will be performed on stool samples to identify associated changes in microbiome absolute abundance at the genus and species level. | baseline |
| Quantify absolute abundance of gut microbiome using metagenomic analysis after neoadjuvant chemotherapy treatment |
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Inclusion Criteria:
Exclusion Criteria:
Female only
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Kate Randolph, BS | Contact | 409-223-7891 | kmrandol@utmb.edu | |
| Christopher Danesi, MA | Contact | 409-772-8126 | cpdanesi@utmb.edu |
| Name | Affiliation | Role |
|---|---|---|
| Melinda Sheffield-Moore, PhD | University of Texas | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The University of Texas Medical Branch | Galveston | Texas | 77555 | United States |
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| ID | Term |
|---|---|
| D009369 | Neoplasms |
| D005221 | Fatigue |
| D005222 | Mental Fatigue |
| ID | Term |
|---|---|
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D001526 | Behavioral Symptoms |
| D001519 | Behavior |
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| ID | Term |
|---|---|
| D000068677 | Sildenafil Citrate |
| ID | Term |
|---|---|
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D013450 | Sulfones |
| D013457 |
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The Fatigue and Altered Cognition Scale (FACS) is a joint project from University of Texas Medical Branch and Texas A&M University. The FACS is a 20 question assessment designed to access perceived fatigue and cognition. There are 2 subscales used to calculate a total score. The subscales are: Fatigue and Altered Cognition. The total score is calculated by adding the subscales together. The range of the total score is 0-100, with a higher score indicating more fatigue and altered cognition.
| through radiation treatment completion, average of 30 weeks from baseline |
| Fatigue and Cognition as measured by the Fatigue and Altered Cognition Scale after chemotherapy treatment | The Fatigue and Altered Cognition Scale (FACS) is a joint project from University of Texas Medical Branch and Texas A&M University. The FACS is a 20 question assessment designed to access perceived fatigue and cognition. There are 2 subscales used to calculate a total score. The subscales are: Fatigue and Altered Cognition. The total score is calculated by adding the subscales together. The range of the total score is 0-100, with a higher score indicating more fatigue and altered cognition. | through chemotherapy treatment completion, average of 50 weeks from baseline |
| Fatigue and Cognition as measured by the Fatigue and Altered Cognition Scale after 24 weeks of endocrine treatment | The Fatigue and Altered Cognition Scale (FACS) is a joint project from University of Texas Medical Branch and Texas A&M University. The FACS is a 20 question assessment designed to access perceived fatigue and cognition. There are 2 subscales used to calculate a total score. The subscales are: Fatigue and Altered Cognition. The total score is calculated by adding the subscales together. The range of the total score is 0-100, with a higher score indicating more fatigue and altered cognition. | through 24 weeks of endocrine treatment, average of 74 weeks from baseline |
| Perceived Cognition measured by the Functional Assessment of Cancer Therapy - Cognitive (FACT-Cog) at baseline | The FACT-Cog is a self-administered measure of perceived cognitive impairment for patients undergoing cancer therapy. The FACT-Cog (version 3) contains 37 items which quantify 4 subscale domains using a 5 point Likert-type scale including: perceived cognitive impairments, impact of perceived cognitive impairments on quality of life, comments from others and perceived cognitive abilities. Perceived cognitive impairments subscale will be reported (range: 0-72, with a higher score indicating better quality of life). | baseline |
| Perceived Cognition measured by the Functional Assessment of Cancer Therapy - Cognitive (FACT-Cog) after neoadjuvant chemotherapy treatment | The FACT-Cog is a self-administered measure of perceived cognitive impairment for patients undergoing cancer therapy. The FACT-Cog (version 3) contains 37 items which quantify 4 subscale domains using a 5 point Likert-type scale including: perceived cognitive impairments, impact of perceived cognitive impairments on quality of life, comments from others and perceived cognitive abilities. Perceived cognitive impairments subscale will be reported (range: 0-72, with a higher score indicating better quality of life). | through neoadjuvant chemotherapy treatment completion, average of 20 weeks from baseline |
| Perceived Cognition measured by the Functional Assessment of Cancer Therapy - Cognitive (FACT-Cog) after surgery | The FACT-Cog is a self-administered measure of perceived cognitive impairment for patients undergoing cancer therapy. The FACT-Cog (version 3) contains 37 items which quantify 4 subscale domains using a 5 point Likert-type scale including: perceived cognitive impairments, impact of perceived cognitive impairments on quality of life, comments from others and perceived cognitive abilities. Perceived cognitive impairments subscale will be reported (range: 0-72, with a higher score indicating better quality of life). | through completion of surgery, average of 24 weeks from baseline |
| Perceived Cognition measured by the Functional Assessment of Cancer Therapy - Cognitive (FACT-Cog) after radiation treatment | The FACT-Cog is a self-administered measure of perceived cognitive impairment for patients undergoing cancer therapy. The FACT-Cog (version 3) contains 37 items which quantify 4 subscale domains using a 5 point Likert-type scale including: perceived cognitive impairments, impact of perceived cognitive impairments on quality of life, comments from others and perceived cognitive abilities. Perceived cognitive impairments subscale will be reported (range: 0-72, with a higher score indicating better quality of life). | through radiation treatment completion, average of 30 weeks from baseline |
| Perceived Cognition measured by the Functional Assessment of Cancer Therapy - Cognitive (FACT-Cog) after chemotherapy treatment | The FACT-Cog is a self-administered measure of perceived cognitive impairment for patients undergoing cancer therapy. The FACT-Cog (version 3) contains 37 items which quantify 4 subscale domains using a 5 point Likert-type scale including: perceived cognitive impairments, impact of perceived cognitive impairments on quality of life, comments from others and perceived cognitive abilities. Perceived cognitive impairments subscale will be reported (range: 0-72, with a higher score indicating better quality of life). | through chemotherapy treatment completion, average of 50 weeks from baseline |
| Perceived Cognition measured by the Functional Assessment of Cancer Therapy - Cognitive (FACT-Cog) after 24 weeks of endocrine therapy treatment | The FACT-Cog is a self-administered measure of perceived cognitive impairment for patients undergoing cancer therapy. The FACT-Cog (version 3) contains 37 items which quantify 4 subscale domains using a 5 point Likert-type scale including: perceived cognitive impairments, impact of perceived cognitive impairments on quality of life, comments from others and perceived cognitive abilities. Perceived cognitive impairments subscale will be reported (range: 0-72, with a higher score indicating better quality of life). | through 24 weeks of endocrine treatment, average of 74 weeks from baseline |
| Perceptual Fatigue as measured by the MD Anderson Brief Fatigue Inventory (BFI) at baseline | Perceptual fatigue will be assessed using the Brief Fatigue Inventory (BFI), a 9-item questionnaire that assesses perceptual fatigue as well as fatigue interferences (e.g. interference with enjoyment of life). The scores from all 9 questions can be average to calculate a Global Fatigue Score, with a range from 0 to 10, with a higher score indicating more fatigue. | baseline |
| Perceptual Fatigue as measured by the MD Anderson Brief Fatigue Inventory (BFI) after neoadjuvant chemotherapy treatment | Perceptual fatigue will be assessed using the Brief Fatigue Inventory (BFI), a 9-item questionnaire that assesses perceptual fatigue as well as fatigue interferences (e.g. interference with enjoyment of life). The scores from all 9 questions can be average to calculate a Global Fatigue Score, with a range from 0 to 10, with a higher score indicating more fatigue. | through neoadjuvant chemotherapy treatment completion, average of 20 weeks from baseline |
| Perceptual Fatigue as measured by the MD Anderson Brief Fatigue Inventory (BFI) after surgery | Perceptual fatigue will be assessed using the Brief Fatigue Inventory (BFI), a 9-item questionnaire that assesses perceptual fatigue as well as fatigue interferences (e.g. interference with enjoyment of life). The scores from all 9 questions can be average to calculate a Global Fatigue Score, with a range from 0 to 10, with a higher score indicating more fatigue. | through completion of surgery, average of 24 weeks from baseline |
| Perceptual Fatigue as measured by the MD Anderson Brief Fatigue Inventory (BFI) after radiation treatment | Perceptual fatigue will be assessed using the Brief Fatigue Inventory (BFI), a 9-item questionnaire that assesses perceptual fatigue as well as fatigue interferences (e.g. interference with enjoyment of life). The scores from all 9 questions can be average to calculate a Global Fatigue Score, with a range from 0 to 10, with a higher score indicating more fatigue. | through radiation treatment completion, average of 30 weeks from baseline |
| Perceptual Fatigue as measured by the MD Anderson Brief Fatigue Inventory (BFI) after chemotherapy treatment | Perceptual fatigue will be assessed using the Brief Fatigue Inventory (BFI), a 9-item questionnaire that assesses perceptual fatigue as well as fatigue interferences (e.g. interference with enjoyment of life). The scores from all 9 questions can be average to calculate a Global Fatigue Score, with a range from 0 to 10, with a higher score indicating more fatigue. | through chemotherapy treatment completion, average of 50 weeks from baseline |
| Perceptual Fatigue as measured by the MD Anderson Brief Fatigue Inventory (BFI) after 24 weeks of endocrine treatment | Perceptual fatigue will be assessed using the Brief Fatigue Inventory (BFI), a 9-item questionnaire that assesses perceptual fatigue as well as fatigue interferences (e.g. interference with enjoyment of life). The scores from all 9 questions can be average to calculate a Global Fatigue Score, with a range from 0 to 10, with a higher score indicating more fatigue. | through 24 weeks of endocrine treatment, average of 74 weeks from baseline |
Metagenomic analysis using a custom PCR array will be performed on stool samples to identify associated changes in microbiome absolute abundance at the genus and species level. |
| through neoadjuvant chemotherapy treatment completion, average of 20 weeks from baseline |
| Quantify absolute abundance of gut microbiome using metagenomic analysis after surgery | Metagenomic analysis using a custom PCR array will be performed on stool samples to identify associated changes in microbiome absolute abundance at the genus and species level. | through completion of surgery, average of 24 weeks from baseline |
| Quantify absolute abundance of gut microbiome using metagenomic analysis after radiation treatment | Metagenomic analysis using a custom PCR array will be performed on stool samples to identify associated changes in microbiome absolute abundance at the genus and species level. | through radiation treatment completion, average of 30 weeks from baseline |
| Quantify absolute abundance of gut microbiome using metagenomic analysis after chemotherapy treatment | Metagenomic analysis using a custom PCR array will be performed on stool samples to identify associated changes in microbiome absolute abundance at the genus and species level. | through chemotherapy treatment completion, average of 50 weeks from baseline |
| Quantify absolute abundance of gut microbiome using metagenomic analysis after 24 weeks of endocrine treatment | Metagenomic analysis using a custom PCR array will be performed on stool samples to identify associated changes in microbiome absolute abundance at the genus and species level. | through 24 weeks of endocrine treatment, average of 74 weeks from baseline |
| Fold change in relative abundance of gut microbiome using using metatranscriptomic analysis from baseline to after neoadjuvant chemotherapy treatment | Metatranscriptomic analysis using a RNA seq will be performed on stool samples to identify associated fold changes in which genes are turned on and off | through neoadjuvant chemotherapy treatment completion, average of 20 weeks from baseline |
| Fold change in relative abundance of gut microbiome using using metatranscriptomic analysis from baseline to after surgery | Metatranscriptomic analysis using a RNA seq will be performed on stool samples to identify associated fold changes in which genes are turned on and off | through completion of surgery, average of 24 weeks from baseline |
| Fold change in relative abundance of gut microbiome using using metatranscriptomic analysis from baseline to after radiation treatment | Metatranscriptomic analysis using a RNA seq will be performed on stool samples to identify associated fold changes in which genes are turned on and off | through radiation treatment completion, average of 30 weeks from baseline |
| Fold change in relative abundance of gut microbiome using using metatranscriptomic analysis from baseline to after chemotherapy treatment | Metatranscriptomic analysis using a RNA seq will be performed on stool samples to identify associated fold changes in which genes are turned on and off | through chemotherapy treatment completion, average of 50 weeks from baseline |
| Fold change in relative abundance of gut microbiome using using metatranscriptomic analysis from baseline to after 24 weeks of endocrine treatment | Metatranscriptomic analysis using a RNA seq will be performed on stool samples to identify associated fold changes in which genes are turned on and off | through 24 weeks of endocrine treatment, average of 74 weeks from baseline |
| Sulfur Compounds |
| D010879 | Piperazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |