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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how Sildenafil, commonly used for erectile dysfunction, might address memory and fatigue issues related to breast cancer. Researchers aim to determine if adding Sildenafil to standard cancer treatments can enhance mental clarity and reduce tiredness. The trial seeks women aged 30 to 50 with ER+/HER2- breast cancer who have had their menstrual cycle in the past year. Participants must be willing to follow study procedures and provide consent. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants an opportunity to contribute to potentially groundbreaking treatment advancements.

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 there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that sildenafil, the main ingredient in Viagra, is generally safe for use. It has treated erectile dysfunction for many years and has FDA approval for this purpose. Some studies found that people who took sildenafil were less likely to develop Alzheimer's disease over six years, suggesting it might help protect the brain.

Research on similar drugs, like tadalafil and vardenafil, has also demonstrated improved brain function. These studies used sildenafil in doses up to 100mg, higher than the 50mg daily dose planned for this trial, suggesting the treatment is well-tolerated.

Overall, while any medication can have side effects, existing evidence indicates that sildenafil is safe, especially at the dose planned for this trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for cancer-related cognitive impairment, which typically focus on managing symptoms through cognitive rehabilitation and medications like stimulants or antidepressants, Sildenafil offers a unique approach by using a well-known drug traditionally used for erectile dysfunction. Researchers are excited about Sildenafil because it works by improving blood flow, which could potentially enhance brain function and cognitive abilities. This new mechanism of action sets it apart from existing treatments and might offer quicker or more effective results for patients experiencing cognitive difficulties due to cancer.

What evidence suggests that Sildenafil might be an effective treatment for cancer-related cognitive impairment?

Research has shown that Sildenafil, a drug often used for erectile dysfunction, might also aid brain function. Studies have found that Sildenafil can improve memory and learning when the brain is under stress, such as after a stroke. Some research suggests it might reduce the risk of Alzheimer's, a disease affecting memory and thinking. Although conducted in various contexts, these studies indicate that Sildenafil could help with cognitive problems related to cancer treatments. In this trial, participants will receive either standard care alone or standard care combined with Sildenafil. This approach might be useful for "chemobrain," a term for the mental fog and memory issues some cancer patients experience. ^{1 2 5 6 7}

Who Is on the Research Team?

Melinda Sheffield-Moore, PhD

Principal Investigator

University of Texas

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. trialx.com trialx.com/clinical-trials/listings/309170/sildenafil-to-prevent-and-reduce-cancer-related-cognitive-impairment/

Sildenafil to Prevent and Reduce Cancer Related ... 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 ...

2. withpower.com withpower.com/trial/sildenafil-for-cancer-related-cognitive-impairment-e598d

Sildenafil for Cancer-Related Cognitive Impairment 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 ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10977448/

Sildenafil as a Candidate Drug for Alzheimer's Disease We showed that sildenafil usage is associated with reduced likelihood of AD across four new drug compactor cohorts, including bumetanide, furosemide, ...

4. mdpi.com mdpi.com/2227-9059/12/9/2077

Effects of Sildenafil on Cognitive Function Recovery and ... Sildenafil treatment improved long-term memory, spatial learning, and memory impairment caused by transient global cerebral ischemia. In the Barnes maze test ...

5. embopress.org embopress.org/doi/10.15252/emmm.202012075

Cellular mechanisms and treatments for chemobrain Chemotherapy is a life‐saving treatment for cancer patients, but also causes long‐term cognitive impairment, or “chemobrain”, in survivors.

6. nih.gov nih.gov/news-events/nih-research-matters/viagra-associated-reduced-risk-alzheimers-disease

Viagra associated with reduced risk of Alzheimer's disease They found that the people (mostly men) who took sildenafil were 69% less likely to develop AD over 6 years than those who did not take the drug ...

7. alzdiscovery.org alzdiscovery.org/uploads/cognitive_vitality_media/PDE5-inhibitors-Cognitive-Vitality-For-Researchers.pdf

PDE5 inhibitors (tadalafil, sildenafil, vardenafil) Two small human studies in men have reported improved cognitive function with PDE5 inhibition. In young, healthy men, an acute high dose of sildenafil (100mg) ...