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

Phase III, Randomized, Double-blind, Placebo-controlled Study Investigating the Efficacy of Creatine Supplementation in Attenuating Chemotherapy-related Cognitive Decline in Patients With Early-stage Breast Cancer Undergoing Chemotherapy.

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

Study Overview

• Status: Not yet recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Other: Placebo; Drug: Creatine

• Study Type: Interventional
• Enrollment (Estimated): 227
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Intituto D'Or de Pesquisa e Ensino São Paulo; Phone Number: pesquisaclinica@idor.org; Email: oncologia.projetos@idor.org

Study Locations

• Brazil
  • São Paulo
    • São Paulo, São Paulo, Brazil
      • Instituto D'Or de Pesquisa e Ensino de São Paulo
      • Contact: Instituto D'Or de Pesquisa e Ensino IDOR; Phone Number: pesquisaclinica@idor.org; Email: oncologia.projetos@idor.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Arm A: Placebo; 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.	Other: Placebo; Oral placebo powder matched in appearance, taste, and packaging to the investigational product, administered once daily dissolved in water. The placebo is initiated 7 days before the start of neoadjuvant or adjuvant chemotherapy and continued through chemotherapy and up to 12 months after chemotherapy completion. The placebo contains no active ingredients and is used as the comparator to assess the preventive effect of creatine supplementation on chemotherapy-related cognitive impairment.
Active Comparator: Arm B: Creatine Supplementation; 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.	Drug: Creatine; Oral creatine monohydrate supplementation administered at a fixed dose of 5 g per day, dissolved in water and taken once daily. The intervention starts 7 days before initiation of neoadjuvant or adjuvant chemotherapy and continues through chemotherapy and up to 12 months after chemotherapy completion. The intervention is designed to evaluate the preventive effect of creatine on chemotherapy-related cognitive impairment, with longitudinal cognitive, clinical, imaging, and translational assessments. The comparator is a matched placebo identical in appearance, taste, and packaging.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in patient-reported cognitive function	Measured by the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog), version 3, from baseline to 1 month after completion of chemotherapy. A clinically significant cognitive decline is defined as a decrease of at least 7.5 points in the total FACT-Cog score.	Baseline and 1 month after completion of chemotherapy

Collaborators and Investigators

• Sponsor: D'Or Institute for Research and Education

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: January 20, 2026
• First Submitted That Met QC Criteria: January 20, 2026
• First Posted (Actual): January 28, 2026

Study Record Updates

• Last Update Posted (Actual): January 28, 2026
• Last Update Submitted That Met QC Criteria: January 20, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Amino Acids, Peptides, and Proteins; Organic Chemicals; Amino Acids; Guanidines; Amidines; Creatine
• Other Study ID Numbers: IARA NUP 25000.193607/2025-11

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No