Breast NeoplasmsEarly Phase 1HPCardiotoxNCT03685175
Using Hyperpolarized [1-13C]Pyruvate to Detect Cardiotoxicity
A Early Phase 1 study testing Formal study using hyperpolarized 13C-pyruvate injection and Feasible study using hyperpolarized 13C-pyruvate injection in people with Breast Neoplasms, run by University of Texas Southwestern Medical Center at 1 site in United States.
Trial summary
The anthracycline doxorubicin, first introduced in the 1960's, continues to be an effectively utilized antineoplastic drug. Even at relatively low cumulative doses there is risk of cardiotoxicity. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Breast Neoplasms
- What is being tested?
- Formal study using hyperpolarized 13C-pyruvate injection and Feasible study using hyperpolarized 13C-pyruvate injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 79 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Jul 2018to 28 Feb 2025
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Female or male with breast cancer tissue diagnosis or a healthy volunteer.
- Plan for treatment as cardiotoxic therapy. Patients for the feasibility study must be post cardiotoxic therapy, and patients for the formal study should not have started the cardiotoxic therapy yet.
- Age ≥ 18 years
- Ability to understand and the willingness to sign a written informed consent
- While all races and ethnicities will be included, subjects must be able to read and speak the English language, and or, the Spanish Language.
- Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
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- A female of childbearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
- Has not undergone a hysterectomy or bilateral oophorectomy; or
- Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
- Males must be surgically sterile or have a female partner using an acceptable method of contraception.
- Acceptable surgical sterilization techniques are vasectomy with surgery at least 6 months prior to dosing. Males must also refrain from sperm donation during the study and for 6 months following discontinuation of treatment.
- Acceptable methods of contraception for female partners of childbearing potential are an intrauterine device, contraceptive implant, and a barrier method (eg. Condom, diaphragm, cervical cap) during the study and for 6 months after patient discontinuation of treatment.
Who cannot join
- Patients for the feasibility study must be post cardiotoxic therapy
- Known Type 1 or Type 2 diabetes.
- Subjects who are receiving any other investigational agents that are not compatible with the study.
- Subjects with known remote, macro, metastases will be excluded from this clinical trial because of their poor prognosis.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Any contraindication per MRI Screening Form (Appendix A attached) including, but not limited to:
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- Metal Implants and devices contraindicated at 3T.
- Breast tissue expanders.
- Non-MR compatible IV port.
- Claustrophobia.
- Female subjects who are already pregnant.
- Sickle cell disease
- Hemolytic anemia
- If the subject agrees to doing a cardiac function MRI scan with gadolinium based contrast agent intravenously:
- eGFR ≤ 30 mL/min/1.73m2
Trial locations and contacts
1 site in 1 country.
United States1 site
UT Southwestern - Advanced Imaging Research Center
Dallas, Texas, 75390
About this study
Official title: Effect of Cardiotoxic Anticancer Therapy on the Metabolism of [1-13C]Pyruvate in Cardiac Mitochondria
The anthracycline doxorubicin, first introduced in the 1960's, continues to be an effectively utilized antineoplastic drug. Even at relatively low cumulative doses there is risk of cardiotoxicity. However, the incidence of subclinical cardiotoxicity is not known, carrying a potential risk for late effects in cancer survivors. Doxorubicin has systemic toxicity that may contribute to cardiac metabolic stress, but the main cardiotoxic mechanism involves cardiac mitochondria. The primary goal of this study is to detect early changes in the mitochondrial metabolism in situ as a marker for subclinical doxorubicin induced cardiotoxicity. The problem of cardiovascular complications following chemotherapy for breast cancer goes far beyond anthracyclines alone. In addition, other agents such as trastuzumab, and pertuzumab and emerging novel therapies may also promote cardiovascular injury. The secondary objective is to test the hypothesis that cardiotoxicity due to other medical anticancer therapies and radiation therapy involving the heart field is associated with a signature of early impaired aerobic cardiac metabolism through pyruvate dehydrogenase.
Read the detailed description
This is a prospective, single-center study in women and men with breast cancer requiring cardiotoxic therapy. The study will be conducted in parallel to the standard clinical care, at dedicated visits.
In this study patients will undergo a cardiac magnetic resonance (MR) signal detection after injection of hyperpolarized carbon-13 pyruvate. The study will be performed before the course of cardiotoxic therapy, and after completing the treatment.
Patients will be screened prior to enrollment based on study specific inclusion and exclusion criteria and MRI safety criteria.
On the day of the metabolic cardiac MR scan an IV line will be inserted and the participant will receive a bolus of oral glucose. The ingestion of glucose will be required to prepare the state of the heart for metabolic imaging. Following this preparation the participant will undergo a cardiac MR study of about 45 minutes, including carbon-13 dedicated sequences.
A separate dedicated cardiac MRI session may be completed in certain participants.
Feasibility Study (Part I) : Administration at two visits 1) after completion of cardiotoxic therapy and 2) 1 to 6 months after the first time point following medical therapy (SOC).
Formal Study (Part II) : Administration at two visits: 1) baseline MRI before administration of cardiotoxic therapy and 2) after completion of cardiotoxic therapy.
- Conditions
- Breast Neoplasms
- Being tested
- Formal study using hyperpolarized 13C-pyruvate injection, Feasible study using hyperpolarized 13C-pyruvate injection
- Keywords
- Magnetic Resonance Imaging, Doxorubicin
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Formal study using hyperpolarized 13C-pyruvate injectionDrug
Also called Cardiac MRI with injection of hyperpolarized 13C-pyruvate
Administration at two visits 1) after completion of cardiotoxic therapy and 2) 1 to 6 months after the first time point following medical therapy (SOC)
Feasible study using hyperpolarized 13C-pyruvate injectionDrug
Also called Cardiac MRI with injection of hyperpolarized 13C-pyruvate
Administration at two visits: 1) baseline MRI before administration of cardiotoxic therapy and 2) after completion of cardiotoxic therapy
| Study group | Role | What they receive |
|---|---|---|
| Formal Study | Experimental | Hyperpolarized 13C-pyruvate, is injected into patients before receiving cardiotoxic therapy and immediately after, for a cardiac MRI scan Receives: Drug: Formal study using hyperpolarized 13C-pyruvate injection |
| Feasibility Study | Experimental | Hyperpolarized 13C-pyruvate injection, is given to patients after completing cardiotoxic therapy, and again at 1 to 6 six months after the first cardiac MRI scan Receives: Drug: Feasible study using hyperpolarized 13C-pyruvate injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Detect subclinical anthracycline induced cardiotoxicity using hyperpolarized carbon-13 pyruvate
Detect the correlation between cardiac carbon-13 pyruvate metabolism and cardiac mechanical function at baseline and after exposure to cardiotoxic therapy
Measured: 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Sep 2018
- Study start3 Jul 2018
- Primary completion28 Feb 2025
- Study completion28 Feb 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast NeoplasmsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 79 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Texas Southwestern Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Vlad Zaha, University of Texas Southwestern Medical Center
- Investigators
- Vlad G Zaha, MD, PhD, Principal investigator, Advanced Imaging Research Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03685175
- Sponsor's protocol ID
- STU 072016-058
- Acronym
- HPCardiotox
- Status last verified
- Mar 2025
- First submitted
- 11 Mar 2017
- Last updated
- 30 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Khashami F, Dimitrov IE, Fuetterer M, Gloggler S, Zhang B, Tan E, Kozerke S, Henning A, Hussain T, Malloy CR, Unni N, Zaha VG; CTOX Trial Investigator(s). Optimized Detection of Left Ventricular Hyperpolarized [1-13C]Pyruvate Signal in Human Cardiac Metabolic Imaging. Magn Reson Med. 2026 Jul;96(1):420-434. doi: 10.1002/mrm.70332. Epub 2026 Mar 6.
PubMed 41792944
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Cardiotoxic Anticancer Therapy on the Metabolism of [1-13C]Pyruvate in Cardiac Mitochondria
- ClinicalTrials.gov ID
- NCT03685175
- Acronym / sponsor ID
- HPCardiotox / STU 072016-058
- Conditions
- Breast Neoplasms
- Keywords
- Magnetic Resonance Imaging, Doxorubicin
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 79 participants (actual)
- Lead sponsor
- University of Texas Southwestern Medical CenterUniversity, hospital or other
- Study start
- 3 Jul 2018 (actual)
- Primary completion
- 28 Feb 2025 (actual)
- Study completion
- 28 Feb 2025 (actual)
- First posted
- 26 Sep 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The anthracycline doxorubicin, first introduced in the 1960's, continues to be an effectively utilized antineoplastic drug. Even at relatively low cumulative doses there is risk of cardiotoxicity. However, the incidence of subclinical cardiotoxicity is not known, carrying a potential risk for late effects in cancer survivors. Doxorubicin has systemic toxicity that may contribute to cardiac metabolic stress, but the main cardiotoxic mechanism involves cardiac mitochondria. The primary goal of this study is to detect early changes in the mitochondrial metabolism in situ as a marker for subclinical doxorubicin induced cardiotoxicity. The problem of cardiovascular complications following chemotherapy for breast cancer goes far beyond anthracyclines alone. In addition, other agents such as trastuzumab, and pertuzumab and emerging novel therapies may also promote cardiovascular injury. The secondary objective is to test the hypothesis that cardiotoxicity due to other medical anticancer therapies and radiation therapy involving the heart field is associated with a signature of early impaired aerobic cardiac metabolism through pyruvate dehydrogenase.
Detailed description
This is a prospective, single-center study in women and men with breast cancer requiring cardiotoxic therapy. The study will be conducted in parallel to the standard clinical care, at dedicated visits.
In this study patients will undergo a cardiac magnetic resonance (MR) signal detection after injection of hyperpolarized carbon-13 pyruvate. The study will be performed before the course of cardiotoxic therapy, and after completing the treatment.
Patients will be screened prior to enrollment based on study specific inclusion and exclusion criteria and MRI safety criteria.
On the day of the metabolic cardiac MR scan an IV line will be inserted and the participant will receive a bolus of oral glucose. The ingestion of glucose will be required to prepare the state of the heart for metabolic imaging. Following this preparation the participant will undergo a cardiac MR study of about 45 minutes, including carbon-13 dedicated sequences.
A separate dedicated cardiac MRI session may be completed in certain participants.
Feasibility Study (Part I) : Administration at two visits 1) after completion of cardiotoxic therapy and 2) 1 to 6 months after the first time point following medical therapy (SOC).
Formal Study (Part II) : Administration at two visits: 1) baseline MRI before administration of cardiotoxic therapy and 2) after completion of cardiotoxic therapy.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Formal Study | Experimental | Drug: Formal study using hyperpolarized 13C-pyruvate injectionHyperpolarized 13C-pyruvate, is injected into patients before receiving cardiotoxic therapy and immediately after, for a cardiac MRI scan |
| Feasibility Study | Experimental | Drug: Feasible study using hyperpolarized 13C-pyruvate injectionHyperpolarized 13C-pyruvate injection, is given to patients after completing cardiotoxic therapy, and again at 1 to 6 six months after the first cardiac MRI scan |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Female or male with breast cancer tissue diagnosis or a healthy volunteer.
- Plan for treatment as cardiotoxic therapy. Patients for the feasibility study must be post cardiotoxic therapy, and patients for the formal study should not have started the cardiotoxic therapy yet.
- Age ≥ 18 years
- Ability to understand and the willingness to sign a written informed consent
- While all races and ethnicities will be included, subjects must be able to read and speak the English language, and or, the Spanish Language.
Key exclusion criteria (15 listed)
- Patients for the feasibility study must be post cardiotoxic therapy
- Known Type 1 or Type 2 diabetes.
- Subjects who are receiving any other investigational agents that are not compatible with the study.
- Subjects with known remote, macro, metastases will be excluded from this clinical trial because of their poor prognosis.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Formal study using hyperpolarized 13C-pyruvate injectionAlso: Cardiac MRI with injection of hyperpolarized 13C-pyruvateAdministration at two visits 1) after completion of cardiotoxic therapy and 2) 1 to 6 months after the first time point following medical therapy (SOC) | Drug | Formal Study |
| Feasible study using hyperpolarized 13C-pyruvate injectionAlso: Cardiac MRI with injection of hyperpolarized 13C-pyruvateAdministration at two visits: 1) baseline MRI before administration of cardiotoxic therapy and 2) after completion of cardiotoxic therapy | Drug | Feasibility Study |
Primary outcome
Detect subclinical anthracycline induced cardiotoxicity using hyperpolarized carbon-13 pyruvate
Time frame: 4 years
Detect the correlation between cardiac carbon-13 pyruvate metabolism and cardiac mechanical function at baseline and after exposure to cardiotoxic therapy
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2025.
- Derived from this study: PubMed 41792944Khashami F, Dimitrov IE, Fuetterer M, Gloggler S, Zhang B, Tan E, Kozerke S, Henning A, Hussain T, Malloy CR, Unni N, Zaha VG; CTOX Trial Investigator(s). Optimized Detection of Left Ventricular Hyperpolarized [1-13C]Pyruvate Signal in Human Cardiac Metabolic Imaging. Magn Reson Med. 2026 Jul;96(1):420-434. doi: 10.1002/mrm.70332. Epub 2026 Mar 6.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Vlad G Zaha, MD, PhD principal investigator
Advanced Imaging Research Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Formal study using hyperpolarized 13C-pyruvate injection and Feasible study using hyperpolarized 13C-pyruvate injection in people with Breast Neoplasms, run by University of Texas Southwestern Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Detect subclinical anthracycline induced cardiotoxicity using hyperpolarized carbon-13 pyruvate (time frame: 4 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03685175, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Mar 2025.