Sildenafil to Prevent and Reduce Cancer Related Cognitive Impairment

Last updated: November 17, 2025
Sponsor: The University of Texas Medical Branch, Galveston
Overall Status: Active - Not Recruiting

Phase

2/3

Condition

Memory Loss

Neoplasms

Mild Cognitive Impairment

Treatment

Sildenafil

Clinical Study ID

NCT06800092
24-0247
  • Ages 30-50
  • Female

Study 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.

Eligibility Criteria

Inclusion

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

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 afterrepeated evaluation with proper cuff. This range is the acceptable range stated inthe 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 thesubject at increased risk for participation

Study Design

Total Participants: 30
Treatment Group(s): 1
Primary Treatment: Sildenafil
Phase: 2/3
Study Start date:
March 15, 2026
Estimated Completion Date:
June 01, 2030

Study 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.

Connect with a study center

  • The University of Texas Medical Branch

    Galveston, Texas 77555
    United States

    Site Not Available

  • The University of Texas Medical Branch

    Galveston 4692883, Texas 4736286 77555
    United States

    Site Not Available

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