Creatine and Cognitive Health in Patients With Early-stage Breast Cancer During and After Chemotherapy Treatment (IARA)

D'Or Institute for Research and Education

Status and phase: Begins enrollment in 5 months; Phase 3

Conditions: Breast Cancer

Treatments: Other: Placebo; Drug: Creatine

Study type: Interventional

Funder types: Other

Identifiers

NCT07372144

IARA NUP 25000.193607/2025-11

Details and patient eligibility

About

The goal of this clinical trial is to evaluate whether oral creatine supplementation can prevent chemotherapy-related cognitive impairment in patients with early-stage breast cancer undergoing neoadjuvant or adjuvant chemotherapy. The main questions it aims to answer are:

• Does creatine supplementation reduce the occurrence and severity of chemotherapy-related cognitive impairment, as measured by patient-reported cognitive function?
• Does creatine supplementation preserve objective cognitive performance compared with placebo during and after chemotherapy?

Researchers will compare creatine supplementation (5 g/day) with placebo to assess differences in cognitive outcomes, safety, and exploratory biological markers.

Participants will:

• Receive oral creatine or placebo starting 7 days before chemotherapy and continuing until 12 months after chemotherapy completion
• Complete patient-reported cognitive assessments and objective neuropsychological tests at predefined time points
• Undergo clinical follow-up for safety and oncologic outcomes
• Provide blood samples for biomarker analyses and stool samples for gut microbiota assessment
• Undergo brain magnetic resonance imaging at selected study visits

Enrollment: 227 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age ≥18 years.
• Histologically confirmed invasive breast cancer (stages I-III).
• Indication for neoadjuvant or adjuvant chemotherapy containing an anthracycline or a taxane.
• Targeted therapies and hormone therapy are permitted according to clinical indication.
• Ability to provide informed consent and comply with study procedures.
• ECOG performance status 0-2.
• Ability to maintain adequate hydration.

Exclusion criteria

• Prior neurologic conditions that may impair cognitive assessment, including previous stroke, dementia, traumatic brain injury with neurologic sequelae, or other neurologic disorders affecting cognition.
• Uncorrected sensory impairments that preclude cognitive assessment and/or completion of study instruments.
• History of uncontrolled psychiatric disorders that may interfere with cognitive evaluation.
• Creatinine clearance <60 mL/min, calculated using the Cockcroft-Gault formula.
• Known liver disease.
• Pregnancy.
• Heart failure.
• Presence of ascites.
• Inflammatory bowel disease.
• Chronic use of nonsteroidal anti-inflammatory drugs (NSAIDs).
• Lactation.
• Chronic use of immunosuppressive agents, including doses greater than 10 mg/day or equivalent.
• Prior chronic creatine supplementation within the last 3 months.
• Known allergy to any component of the supplement or placebo.

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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227 participants in 2 patient groups, including a placebo group

Arm A: Placebo

Placebo Comparator group

Description:

Participants assigned to this arm will receive a placebo powder matched in appearance, taste, and packaging to the investigational product. The placebo will be administered orally once daily, dissolved in water, starting 7 days before the first cycle of chemotherapy and continuing until 12 months after completion of chemotherapy.

Treatment:

Other: Placebo

Arm B: Creatine Supplementation

Active Comparator group

Description:

Participants assigned to this arm will receive oral creatine monohydrate at a dose of 5 g per day, dissolved in water and administered once daily. Treatment will begin 7 days before the first cycle of chemotherapy and will continue until 12 months after completion of chemotherapy.

Treatment:

Drug: Creatine