Sildenafil for Cancer-Related Cognitive Impairment

(SPARC Trial)

Overseen By Kate Randolph, BS

Age: 18 - 65

Sex: Female

Trial Phase: Phase 2 & 3

Sponsor: The University of Texas Medical Branch, Galveston

Must not be taking: Alpha blockers, PDE5 inhibitors, Nitrates

Disqualifiers: Untreated thyroid, Diabetes, BMI >30, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

30 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

You may need to stop taking certain medications, such as alpha blockers, PDE5 inhibitors, and nitrates, as they are not allowed in the trial. The protocol does not specify other medications, so it's best to discuss your current medications with the study team.

Is Sildenafil safe for humans?

Sildenafil, commonly known as Viagra, has been widely used and studied for treating erectile dysfunction and pulmonary hypertension (high blood pressure in the lungs). It is generally considered safe for these conditions, but like any medication, it can have side effects such as headaches, flushing, or upset stomach. Always consult with a healthcare provider for personalized advice. ^{1 2 3 4 5}

How does the drug Sildenafil differ from other treatments for cancer-related cognitive impairment?

Sildenafil, commonly known for treating erectile dysfunction, is unique in this context as it may improve blood flow and potentially enhance cognitive function, unlike traditional treatments for cancer-related cognitive impairment which often focus on managing symptoms with stimulants or mood stabilizers. ^{1 2 6 7 8}

Research Team

Melinda Sheffield-Moore, PhD

Principal Investigator

University of Texas

Eligibility Criteria

This trial is for women aged 30-50 with ER+/HER2- breast cancer who've had a menstrual cycle in the past year and can follow study procedures. Excluded are those with untreated diabetes or thyroid issues, high BMI, certain medical devices, neuromuscular diseases, prior cognitive impairment or chemotherapy, severe claustrophobia, specific medication use recently (alpha blockers, PDE5 inhibitors), extreme blood pressure levels, neurovascular disease or HIV/Hepatitis.

Inclusion Criteria

Self-reported menses occurrence within past 12 months

My breast cancer is ER positive and HER2 negative.

Willing and able to provide consent

Exclusion Criteria

I have diabetes that has not been treated.

My BMI is over 30.

I have a thyroid condition that hasn't been treated.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Chemotherapy

Participants receive neoadjuvant chemotherapy treatment

20 weeks

Surgery

Participants undergo surgery as part of the standard of care treatment

4 weeks

Radiation Treatment

Participants receive radiation treatment

6 weeks

Chemotherapy

Participants receive chemotherapy treatment

20 weeks

Endocrine Treatment

Participants receive 24 weeks of endocrine treatment

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Sildenafil

Trial Overview The study investigates how standard cancer care combined with Sildenafil affects fatigue related to cancer treatment, cognitive function and gut microbiome health in young women undergoing treatment for breast cancer.

Participant Groups

Group I: Standard of Care Treatment and Sildenafil Experimental Treatment 1 Intervention

Sildenafil, 50mg, daily for duration of the standard of care treatment

Group II: Standard of Care Treatment Active Control 1 Intervention

standard of care treatment

Who Is Running the Clinical Trial?

The University of Texas Medical Branch, Galveston

Lead Sponsor

Trials

263

Recruited

55,400+

Findings from Research

Recent prospective trials indicate that patients undergoing chemotherapy can experience specific cognitive impairments, challenging previous beliefs that such dysfunction was not linked to cancer therapy.

Two case studies from a Geriatric Oncology clinic illustrate this issue: a 75-year-old male with lung cancer reported forgetfulness after chemotherapy, and a 65-year-old female with breast cancer experienced cognitive issues following multiple treatments, highlighting the need for awareness and assessment of cognitive health in older cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The impact of cancer therapy on cognition in the elderly. Mandilaras, V., Wan-Chow-Wah, D., Monette, J., et al.[2021]

Two male patients with multiple myeloma experienced severe cognitive impairment while undergoing treatment with lenalidomide, indicating a potential link between the drug and cognitive dysfunction.

Withdrawal of lenalidomide led to recovery of normal cognitive function in one patient, while the other experienced persistent mild cognitive impairment, suggesting that lenalidomide may cause episodic memory issues in some individuals, particularly those with certain risk factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Memory loss during lenalidomide treatment: a report on two cases. Rollin-Sillaire, A., Delbeuck, X., Pollet, M., et al.[2021]

Chemotherapy can lead to cognitive impairments in cancer patients, often referred to as 'chemobrain' or 'chemofog', which affects their mental clarity and memory.

Identifying specific chemotherapy agents responsible for these cognitive issues is crucial for developing effective interventions to prevent or reduce chemotherapy-induced cognitive impairment (CICI).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy-Induced Cognitive Impairment. Kinsley, K., Pritchett, W.[2023]

Cognitive dysfunction is a significant issue for cancer patients, affecting their multitasking, memory, and attention even after treatment, with potential causes including neurotoxic effects of therapy and immune dysregulation.

While pharmacologic treatments for cognitive issues in cancer survivors are limited, nonpharmacologic approaches like cognitive rehabilitation programs are being researched as promising management strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of cancer treatment on cognitive function. Asher, A., Myers, JS.[2022]

Cognitive impairment is a common and significant issue for cancer survivors, affecting their daily functioning and quality of life, yet it is often overlooked and not adequately treated.

This article reviews various interventions aimed at addressing cognitive impairment in cancer survivors, providing recommendations for practice and highlighting the need for further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evidence-based interventions for cancer- and treatment-related cognitive impairment. Von Ah, D., Jansen, CE., Allen, DH.[2022]

A systematic review of 31 studies found that various interventions, such as cognitive behavioral therapy and brain training, show promise in improving cognitive function in cancer patients experiencing cognitive impairment after chemotherapy.

The study highlighted inconsistencies in outcome measurements across different interventions, suggesting a need for standardized assessment tools in future research to better evaluate the effectiveness of these cognitive enhancement strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interventions promoting cognitive function in patients experiencing cancer related cognitive impairment: A systematic review. Oldacres, L., Hegarty, J., O'Regan, P., et al.[2023]

Cancer treatments, particularly chemotherapy and radiotherapy, can lead to cognitive dysfunction due to their cytotoxic effects, which may impair neurogenesis and affect memory and mood.

Several emerging pharmacotherapies, including stimulants like modafinil and methylphenidate, as well as anti-Alzheimer's drugs like memantine and donepezil, are being investigated to help alleviate cognitive dysfunction in cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging pharmacotherapy for cancer patients with cognitive dysfunction. Davis, J., Ahlberg, FM., Berk, M., et al.[2022]

A significant number of cancer patients experience cognitive decline, often referred to as 'chemobrain' or 'chemofog', which was traditionally thought to be solely due to chemotherapy's neurotoxic effects.

Current research indicates that cognitive impairment in cancer patients, now termed 'cancer-related cognitive impairment' (CRCI), is a complex issue influenced by both the cancer itself and its treatments, rather than just the effects of chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[An overview of the research of cancer-related cognitive impairment]. Ferencz, V., S Nagy, Z., Tóth, M.[2019]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

The impact of cancer therapy on cognition in the elderly. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Memory loss during lenalidomide treatment: a report on two cases. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Chemotherapy-Induced Cognitive Impairment. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

The effect of cancer treatment on cognitive function. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Evidence-based interventions for cancer- and treatment-related cognitive impairment. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Interventions promoting cognitive function in patients experiencing cancer related cognitive impairment: A systematic review. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Emerging pharmacotherapy for cancer patients with cognitive dysfunction. [2022]

8. Hungary pubmed.ncbi.nlm.nih.gov

[An overview of the research of cancer-related cognitive impairment]. [2019]