Effects of Creatine Supplementation in Breast Cancer Survivors

Study Overview
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Brief Summary
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The purpose of this study is to test the hypothesis that creatine will accelerate adaptations associated with exercise in breast cancer survivors recently completing chemotherapy.

Detailed Description
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The primary objective of this study is to determine the effects of creatine supplementation in modulating strength and physical function in breast cancer survivors that have recently completed chemotherapy. The primary hypothesis for this objective is that creatine will lead to significantly greater gains in strength and physical function in breast cancer survivors compared to exercise alone. The secondary objective is to determine if supplemental creatine can increase intramuscular storage of creatine and alter energy storage. The hypothesis for this objective is that creatine supplementation will significantly increase intramuscular concentrations of creatine (Cr), phosphocreatine (PCr) and adenosine triphosphate (ATP) in the vastus lateralis (VL) compared to controls. The secondary hypothesis for this objective is that the creatine group will have significantly greater muscle cross-sectional area and significantly lower intramuscular fat compared to controls. The final objective for this study is to test the hypothesis that creatine supplementation will improve body composition in breast cancer survivors.

Official Title
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The THRIVE Study: An Open-Label Randomized Trial of Exercise ± Creatine Supplementation to Augment the Adaptations of Exercise Training in Breast Cancer Survivors

Conditions
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Exercise, Breast Cancer, Chemotherapy Effect, Muscle Weakness, Muscle Loss

Intervention / Treatment
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* Dietary Supplement: Creatine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-75 years of age Recent (within 6 months) completion of chemotherapy Willing to attend 3 virtual exercise sessions per week Able to take oral medications Participant is willing and able to provide consent to participating in the study Serum creatinine ≤ 1.5 x ULN or Estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2 by Chronic Kidney Disease Epidemiology Collaboration equation. Exclusion Criteria: Physical indications where performing exercise may be limited and/or contraindicated Poorly-controlled hypertension (blood pressure > 160/95mmHg) Current tobacco use (within 6 months) Anabolic steroids use Pitting edema Currently undergoing chemotherapy History of moderate-severe heart disease (New York Heart Classification greater than grade II) or pulmonary disease (dyspnea on exertion upon climbing one flight of stairs or less; abnormal breath sounds on auscultation). Pregnant or plan to get pregnant during the study Recent (within one month) or anticipated treatment with corticosteroids (except for short term use during the time of chemotherapy), androgens, progestational agents, or other appetite stimulants Serum creatinine > 1.5 x ULN or Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 by Chronic Kidney Disease Epidemiology Collaboration equation. Currently taking creatine supplements

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This study plans to enroll 30 breast cancer patients who have completed chemotherapy within 6 months prior to consenting for this study. Patients eligible to participate in this study will be allocated to either the creatine group or the control group (1:1) based on a pre-determined randomization list. Each arm will have 15 participants. One arm will receive creatine and the other will serve as the control group with no creatine.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Creatine Supplement Group<br>Participants will engage in three center-based exercise sessions each week for 12 weeks; each session lasting roughly 1-hour. Participants will be given a fitbit (electronic watch that measures steps or heart rate) as well to track heart rate and monitor activity throughout the study. | Dietary Supplement: Creatine<br>* Those randomized to receive creatine (experimental group) will be initially dosed at 20 g/day for 7 days to boost availability of creatine systemically. Thereafter, the dose will be reduced to 5 g/day for maintenance through the duration of the 12-week protocol.<br>|
| No Intervention: Exercise Only Control Group<br>Participants will not participate in the creatine intervention (creatine supplementation). Participants will engage in three center-based exercise sessions each week for 12 weeks; each session lasting roughly 1-hour. Exercise sessions will be held by trained study staff held at the Medical Arts and Research Center Physical Therapy clinic (address listed above). | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in strength in breast cancer survivors | Participants will be evaluated for knee extensor strength via isometric maximum voluntary contraction at approximately 60° knee flexion. | From baseline to 12 weeks | 
| Change in functional capacity in breast cancer survivors | Functional exercise capacity will be assessed via the 6 minute walk test (6MWT). | From baseline to 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in intramuscular creatine and altering energy storage. | Muscle Creatine, Phosphocreatine, and Adenosine-triphosphate content will be assessed in vivo by 31P-MRS using a whole body 3.0T MRI scanner. | From baseline to 12 weeks | 
| Change in muscle cross sectional area | Magnetic resonance imaging will be used to capture the mid-thigh cross section. | From baseline to 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Creatine Supplementation, Magnetic Resonance Spectroscopy, Special Populations, Exercise Oncology