Breast CancerPhase 2NCT05013255
Pioglitazone Therapy Targeting Fatigue in Breast Cancer
A Phase 2 study testing Pioglitazone 15mg and Pioglitazone 30 mg in people with Breast Cancer and Muscle Fatigue, run by West Virginia University at 1 site in United States.
Trial summary
The goal of this project is to evaluate the therapeutic potential of pioglitazone (PIO) to target underlying mechanisms that promote muscle fatigue in patients with breast cancer. This represents an off-label use of this compound, both in terms of the patient population and the clinical phenotype targeted. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer, Muscle Fatigue
- What is being tested?
- Pioglitazone 15mg and Pioglitazone 30 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Dec 2021to Dec 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects must have histologically or cytologically confirmed luminal (ER+/PR+ Her2/neu-) Breast Cancer.
- Subjects must have received no prior therapies besides chemotherapy in the neoadjuvant setting.
- Subject must have a planned surgical (mastectomy) date within 2 weeks of starting treatment.
- 5 Subjects must have normal organ as defined below:
- Hemoglobin within normal institutional limits (or >10?)
- Fasting Blood Glucose within normal institutional limits
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- Serum Creatinine within normal institutional limits
- Liver Function (AST and ALT, Alk phosphatase, Total Bilirubin) within normal limits
- Subject does not have a prior diagnosis of diabetes or currently taking any medications to lower blood glucose levels.
- Subjects must have the ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- Prior diagnosis of Congestive Heart Failure (CHF), Bladder cancer, osteoporosis, bariatric surgery
- Subjects receiving any other investigational agents or known agents to have a major interaction with PIO to include clopidogrel, gatifloxacin, gemfibrozil, leflunomide, lomitapide, lumateperone, mipomersen, pexideartinib and teriflunomide, insulin, Lyrica, Synthroid.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to Pioglitazone.
- Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, unstable angina pectoris, cardiac arrhythmia, active alcoholism or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant or breastfeeding are excluded from this study because Pioglitazone has the potential for teratogenic or abortifacient effects. Because there is an unknown, but potential risk for adverse events in nursing infants secondary to treatment of the mother with PIO, breastfeeding should be discontinued if the mother is treated with PIO. These potential risks may also apply to other agents used in this study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
West Virginia University Cancer Institute
Morgantown, West Virginia, 26506
Kristin Lupinacci, DO, 304-293-1022, kristin.lupinacci@hsc.wvu.edu
About this study
The goal of this project is to evaluate the therapeutic potential of pioglitazone (PIO) to target underlying mechanisms that promote muscle fatigue in patients with breast cancer. This represents an off-label use of this compound, both in terms of the patient population and the clinical phenotype targeted. The central research hypothesis of this study is that daily pioglitazone will restore transcriptional downregulation of pathways within skeletal that promote fatigue.
Read the detailed description
Fatigue is commonly reported in cancer patients, but is not treated due to the absence of viable therapies. At the time of diagnosis, prior to treatment, nearly all breast cancer patients have some degree of muscle dysfunction resulting in fatigue that ranges from mild to debilitating and may worsen with chemotherapy, radiation, and/or surgery. A significant gap in knowledge exists with respect to targetable mechanisms to alleviate fatigue in patients with cancer. The goal of this project is to evaluate the therapeutic potential of pioglitazone (PIO) to target underlying mechanisms that promote muscle fatigue in patients with breast cancer. This represents an off-label use of this compound, both in terms of the patient population and the clinical phenotype targeted. The central research hypothesis of this study is that daily pioglitazone will restore transcriptional downregulation of pathways within skeletal that promote fatigue. The investigators believe this trial will provide the clinical data on optimal PIO dose to affect muscle gene expression in patients with breast cancer. This data will be used to support a larger clinical trial in patients with and without breast cancer to determine PIO therapy effects on muscle fatigue.
Pioglitazone is an FDA-approved drug that is used to treat insulin resistance in patients with diabetes by targeting PPARγ activity, although this drug also affects mitochondrial function through PPARγ regulation. Therefore, the investigators will test the central research hypothesis that daily pioglitazone will restore transcriptional downregulation of pathways within skeletal that promote fatigue. Specific Aim 1 will determine the molecular signature within skeletal muscle in response to low dose and high dose pioglitazone therapy. It is predicted that daily pioglitazone therapy will reverse the breast cancer-associated downregulation of mitochondrial and metabolic genes in skeletal muscle. Specific Aim 2 will determine the effects of low dose and high dose pioglitazone therapy on perceptions of fatigue. It is predicted that daily pioglitazone therapy will improve patient reported perceptions of fatigue.
This is a Phase 2B Trial to determine the lowest effective dose of pioglitazone for affecting skeletal muscle gene expression in breast cancer patients without diabetes (dose-finding study). At the time of registration, subjects will be randomized to either the low dose (15mg PIO; n=10) or the high dose (30mg PIO; n=10) group, or a no-drug control group (n=10). Drug therapy will last for 2 weeks, leading into a scheduled mastectomy. Subjects will be provided with a 2 week supply of PIO on Study Day 1 to be taken orally once per day. Following surgery and muscle biopsy collection subjects will be followed for adverse events, fatigue and body composition for 30 days through their first post-op visit. The total study duration will be 6-weeks (2 weeks of drug treatment + 4 weeks until follow-up visit).
- Conditions
- Breast Cancer, Muscle Fatigue
- Being tested
- Pioglitazone 15mg, Pioglitazone 30 mg
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pioglitazone 15mgDrug
Also called Actos
PIO 15mg orally once daily for 2 weeks
Pioglitazone 30 mgDrug
Also called Actos
PIO 30mg orally once daily for 2 weeks
| Study group | Role | What they receive |
|---|---|---|
| Pioglitazone 15mg Dose | Active comparator | Subjects will be given PIO 15mg once daily, based on the randomization lists prepared by the WVUCI Biostatistics Core. This is a 1:1:1 randomization (10 in each group) without any planned stratification. Receives: Drug: Pioglitazone 15mg |
| Pioglitazone 30mg Dose | Active comparator | Subjects will be given PIO 30mg once daily, based on the randomization lists prepared by the WVUCI Biostatistics Core. This is a 1:1:1 randomization (10 in each group) without any planned stratification. Receives: Drug: Pioglitazone 30 mg |
| No Drug | No intervention | Subjects will be assigned to a no drug control group based on the randomization lists prepared by the WVUCI Biostatistics Core. This is a 1:1:1 randomization (10 in each group) without any planned stratification. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Muscle Gene Expression
evaluate the ability of daily pioglitazone therapy to attenuate the transcriptional downregulation of a gene network within skeletal muscle that is integral to mitochondrial bioenergetics, with PPARγ central to this network. The outcome measure will be RNA-Sequencing and gene expression analysis from muscle biopsies obtained from subjects following either low dose or high dose pioglitazone therapy.
Measured: Up to 6 weeks
Secondary outcomes (2)
Muscle Fatigue
Assess the fatigue in subjects with breast cancer that are being treated with pioglitazone, as measured by the FACT-F questionnaire. 5 point Likert-type scale where 0= Not at all, 1= A little bit, 2= Somewhat, 3= Quite a bit, 4= Very much.
Measured: Up to 6 weeks
Body Weight
Monitor body weight for loss or gains in subjects receiving low dose and high dose pioglitazone for 2 weeks prior to a scheduled mastectomy
Measured: 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Aug 2021
- Study start23 Dec 2021
- Primary completionDec 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by West Virginia UniversityThe sponsor's other registered studies.
- 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
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- West Virginia University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jessica Partin, West Virginia University
- Investigators
- Kristin H Lupinacci, DO, Principal investigator, West Virginia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05013255
- Sponsor's protocol ID
- 2103254164
- Status last verified
- Apr 2025
- First submitted
- 16 Aug 2021
- Last updated
- 8 Apr 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pioglitazone Therapy Targeting Fatigue in Breast Cancer
- ClinicalTrials.gov ID
- NCT05013255
- Acronym / sponsor ID
- 2103254164
- Conditions
- Breast Cancer, Muscle Fatigue
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- West Virginia UniversityUniversity, hospital or other
- Study start
- 23 Dec 2021 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 19 Aug 2021 (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 goal of this project is to evaluate the therapeutic potential of pioglitazone (PIO) to target underlying mechanisms that promote muscle fatigue in patients with breast cancer. This represents an off-label use of this compound, both in terms of the patient population and the clinical phenotype targeted. The central research hypothesis of this study is that daily pioglitazone will restore transcriptional downregulation of pathways within skeletal that promote fatigue.
Detailed description
Fatigue is commonly reported in cancer patients, but is not treated due to the absence of viable therapies. At the time of diagnosis, prior to treatment, nearly all breast cancer patients have some degree of muscle dysfunction resulting in fatigue that ranges from mild to debilitating and may worsen with chemotherapy, radiation, and/or surgery. A significant gap in knowledge exists with respect to targetable mechanisms to alleviate fatigue in patients with cancer. The goal of this project is to evaluate the therapeutic potential of pioglitazone (PIO) to target underlying mechanisms that promote muscle fatigue in patients with breast cancer. This represents an off-label use of this compound, both in terms of the patient population and the clinical phenotype targeted. The central research hypothesis of this study is that daily pioglitazone will restore transcriptional downregulation of pathways within skeletal that promote fatigue. The investigators believe this trial will provide the clinical data on optimal PIO dose to affect muscle gene expression in patients with breast cancer. This data will be used to support a larger clinical trial in patients with and without breast cancer to determine PIO therapy effects on muscle fatigue.
Pioglitazone is an FDA-approved drug that is used to treat insulin resistance in patients with diabetes by targeting PPARγ activity, although this drug also affects mitochondrial function through PPARγ regulation. Therefore, the investigators will test the central research hypothesis that daily pioglitazone will restore transcriptional downregulation of pathways within skeletal that promote fatigue. Specific Aim 1 will determine the molecular signature within skeletal muscle in response to low dose and high dose pioglitazone therapy. It is predicted that daily pioglitazone therapy will reverse the breast cancer-associated downregulation of mitochondrial and metabolic genes in skeletal muscle. Specific Aim 2 will determine the effects of low dose and high dose pioglitazone therapy on perceptions of fatigue. It is predicted that daily pioglitazone therapy will improve patient reported perceptions of fatigue.
This is a Phase 2B Trial to determine the lowest effective dose of pioglitazone for affecting skeletal muscle gene expression in breast cancer patients without diabetes (dose-finding study). At the time of registration, subjects will be randomized to either the low dose (15mg PIO; n=10) or the high dose (30mg PIO; n=10) group, or a no-drug control group (n=10). Drug therapy will last for 2 weeks, leading into a scheduled mastectomy. Subjects will be provided with a 2 week supply of PIO on Study Day 1 to be taken orally once per day. Following surgery and muscle biopsy collection subjects will be followed for adverse events, fatigue and body composition for 30 days through their first post-op visit. The total study duration will be 6-weeks (2 weeks of drug treatment + 4 weeks until follow-up visit).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Pioglitazone 15mg Dose | Active comparator | Drug: Pioglitazone 15mgSubjects will be given PIO 15mg once daily, based on the randomization lists prepared by the WVUCI Biostatistics Core. This is a 1:1:1 randomization (10 in each group) without any planned stratification. |
| Pioglitazone 30mg Dose | Active comparator | Drug: Pioglitazone 30 mgSubjects will be given PIO 30mg once daily, based on the randomization lists prepared by the WVUCI Biostatistics Core. This is a 1:1:1 randomization (10 in each group) without any planned stratification. |
| No Drug | No intervention | –Subjects will be assigned to a no drug control group based on the randomization lists prepared by the WVUCI Biostatistics Core. This is a 1:1:1 randomization (10 in each group) without any planned stratification. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Subjects must have histologically or cytologically confirmed luminal (ER+/PR+ Her2/neu-) Breast Cancer.
- Subjects must have received no prior therapies besides chemotherapy in the neoadjuvant setting.
- Subject must have a planned surgical (mastectomy) date within 2 weeks of starting treatment.
- 5 Subjects must have normal organ as defined below:
- Subject does not have a prior diagnosis of diabetes or currently taking any medications to lower blood glucose levels.
Key exclusion criteria (5 listed)
- Prior diagnosis of Congestive Heart Failure (CHF), Bladder cancer, osteoporosis, bariatric surgery
- Subjects receiving any other investigational agents or known agents to have a major interaction with PIO to include clopidogrel, gatifloxacin, gemfibrozil, leflunomide, lomitapide, lumateperone, mipomersen, pexideartinib and teriflunomide, insulin, Lyrica, Synthroid.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to Pioglitazone.
- Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, unstable angina pectoris, cardiac arrhythmia, active alcoholism or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant or breastfeeding are excluded from this study because Pioglitazone has the potential for teratogenic or abortifacient effects. Because there is an unknown, but potential risk for adverse events in nursing infants secondary to treatment of the mother with PIO, breastfeeding should be discontinued if the mother is treated with PIO. These potential risks may also apply to other agents used in this study.
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 |
|---|---|---|
| Pioglitazone 15mgAlso: ActosPIO 15mg orally once daily for 2 weeks | Drug | Pioglitazone 15mg Dose |
| Pioglitazone 30 mgAlso: ActosPIO 30mg orally once daily for 2 weeks | Drug | Pioglitazone 30mg Dose |
Primary outcome
Muscle Gene Expression
Time frame: Up to 6 weeks
evaluate the ability of daily pioglitazone therapy to attenuate the transcriptional downregulation of a gene network within skeletal muscle that is integral to mitochondrial bioenergetics, with PPARγ central to this network. The outcome measure will be RNA-Sequencing and gene expression analysis from muscle biopsies obtained from subjects following either low dose or high dose pioglitazone therapy.
2 secondary outcomes
Muscle Fatigue
Time frame: Up to 6 weeks
Body Weight
Time frame: 2 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Apr 2025.
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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.
Kristin H Lupinacci, DO principal investigator
West Virginia University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pioglitazone 15mg and Pioglitazone 30 mg in people with Breast Cancer and Muscle Fatigue, run by West Virginia University 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 10 inclusion and 5 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: looking for participants now, as of the sponsor's last update on 8 Apr 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?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Kristin Lupinacci, DO (3042931022, kristin.lupinacci@hsc.wvu.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Muscle Gene Expression (time frame: Up to 6 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 8 Apr 2025.