Sildenafil to Prevent and Reduce Cancer Related Cognitive Impairment

NCT ID: NCT06800092

Last Updated: 2025-11-19

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-03-15
• Study Completion Date: 2030-06-01

Brief Summary

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.

Detailed Description

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.

Conditions

Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: NONE

Study Groups

Standard of Care Treatment

standard of care treatment

Group Type: NO_INTERVENTION

No interventions assigned to this group

Standard of Care Treatment and Sildenafil

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

Group Type: EXPERIMENTAL

Sildenafil

Intervention Type: DRUG

Sildenafil, 50mg, daily

Interventions

Sildenafil

Sildenafil, 50mg, daily

Intervention Type: DRUG

Other Intervention Names

Viagra

Eligibility Criteria

Inclusion Criteria

• Female
• Ages 30 - 50 years
• Self-reported menses occurrence within past 12 months
• Diagnosis of ER+/HER2- breast cancer
• Willing and able to comply with study procedures
• Willing and able to provide consent

Exclusion Criteria

• Untreated thyroid disorder
• Untreated diabetes
• BMI >30
• Current treatment with metformin
• Diagnosed neuromuscular disease
• Diagnosed neurovascular disease
• Prior history of cognitive impairment
• Prior history of chemotherapy treatment
• HIV, Hepatitis B or Hepatitis C
• Systolic blood pressure <90 or >170, diastolic blood pressure <50 or >110 after repeated evaluation with proper cuff. This range is the acceptable range stated in the prescribing information for sildenafil (>90/50 and <170/110)
• Use of alpha blockers in the past 2 weeks
• Use of PDE5 inhibitors in the past 2 weeks
• Use of nitrates
• Subjects with MRI incompatible devices
• Subjects with severe claustrophobia
• Any medical condition that, in the opinion of the investigator, would place the subject at increased risk for participation

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

The University of Texas Medical Branch, Galveston

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Melinda Sheffield-Moore, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Texas

Locations

The University of Texas Medical Branch

Galveston, Texas, United States

Countries

United States

Central Contacts

Kate Randolph, BS

Role: CONTACT

kmrandol@utmb.edu

409-223-7891

Christopher Danesi, MA

Role: CONTACT

cpdanesi@utmb.edu

409-772-8126

Facility Contacts

Kate Randolph, BS

Role: primary

kmrandol@utmb.edu

409-223-7891

Other Identifiers

24-0247

Identifier Type: -

Identifier Source: org_study_id