Sildenafil to Prevent and Reduce Cancer Related Cognitive Impairment (SPARC)

The University of Texas System (UT)

Status and phase

Enrolling

Phase 3

Phase 2

Conditions

Cancer

Treatments

Drug: Sildenafil

Study type

Interventional

Funder types

Other

Identifiers

NCT06800092

24-0247

Details and patient eligibility

About

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.

Full 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.

Enrollment

30 estimated patients

Sex

Female

Ages

30 to 50 years old

Volunteers

No Healthy Volunteers

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