Pioglitazone for Fatigue in Breast Cancer

Overseen By Emidio Pistilli, PhD

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: West Virginia University

Must not be taking: Insulin, Lyrica, Synthroid, others

Disqualifiers: Diabetes, CHF, Bladder cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 2 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if pioglitazone, a medication typically used for other conditions, can reduce muscle fatigue in people with breast cancer. Researchers want to assess its potential benefits in this context. Participants will be divided into groups, with some receiving different doses of the drug and others not receiving it. Suitable candidates have confirmed luminal breast cancer, have only undergone chemotherapy before surgery, and are not currently managing diabetes. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

You may need to stop taking certain medications if they interact with pioglitazone, such as clopidogrel, insulin, and others listed in the trial's exclusion criteria. The protocol does not specify a washout period, but it's important to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that pioglitazone, a drug commonly used for diabetes, is generally well-tolerated. In studies involving patients at high risk for diabetes complications, the side effects of pioglitazone did not prevent treatment continuation, suggesting the drug's safety for long-term use. While this study explores pioglitazone to help with fatigue in breast cancer patients, safety information from diabetes studies can be reassuring. Past research has not found strong links between pioglitazone and an increased risk of breast cancer. As this study is in an early phase, researchers continue to closely monitor its safety for this new purpose. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for fatigue in breast cancer?

Researchers are excited about using Pioglitazone for fatigue in breast cancer patients because it offers a fresh approach to managing this debilitating symptom. Unlike typical treatments for cancer-related fatigue, which often focus on lifestyle changes and managing related conditions, Pioglitazone is a medication that works by targeting insulin resistance and inflammation, potentially addressing the root causes of fatigue. Additionally, Pioglitazone's established safety profile in diabetes management gives researchers confidence in its application for breast cancer-related fatigue. This unique mechanism and safety background set it apart from current options, sparking interest in its potential benefits.

What evidence suggests that pioglitazone might be an effective treatment for fatigue in breast cancer?

Research suggests that pioglitazone might reduce muscle fatigue in breast cancer patients by altering gene activity in muscles. In studies with mice, pioglitazone improved muscle tissues but did not directly reduce muscle fatigue. This trial will evaluate different doses of pioglitazone, with participants receiving either a 15mg or 30mg dose daily, or being assigned to a no-drug control group. The treatment aims to address the root causes of fatigue, which is common in people with breast cancer. Some early findings indicate that taking pioglitazone daily might help patients feel more energetic. Researchers aim to determine if these changes can lead to real-world relief from fatigue for patients. ^{2 6 7 8 9}

Who Is on the Research Team?

Kristin H Lupinacci, DO

Principal Investigator

West Virginia University

Are You a Good Fit for This Trial?

This trial is for individuals with luminal breast cancer (ER+/PR+ Her2/neu-) who have not had any treatments other than chemotherapy. They must have normal organ function, no diabetes or medications affecting blood glucose, and a scheduled mastectomy within two weeks. Pregnant or breastfeeding women, those with heart failure, bladder cancer, osteoporosis, bariatric surgery history or certain illnesses are excluded.

Inclusion Criteria

Subjects must have the ability to understand and the willingness to sign a written informed consent document

I have never been diagnosed with diabetes nor take any blood sugar-lowering medications.

My mastectomy is scheduled within 2 weeks of starting treatment.

Exclusion Criteria

History of allergic reactions attributed to compounds of similar chemical or biologic composition to Pioglitazone

Subjects with uncontrolled intercurrent illness including ongoing or active infection, unstable angina pectoris, cardiac arrhythmia, active alcoholism or psychiatric illness/social situations that would limit compliance with study requirements

I have had congestive heart failure, bladder cancer, osteoporosis, or bariatric surgery.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive daily pioglitazone therapy for 2 weeks prior to scheduled mastectomy

2 weeks

1 visit (in-person) for drug dispensation

Surgery and Biopsy

Participants undergo mastectomy and muscle biopsy collection

1 day

1 visit (in-person)

Follow-up

Participants are monitored for adverse events, fatigue, and body composition for 30 days post-surgery

4 weeks

1 visit (in-person) for follow-up assessment

What Are the Treatments Tested in This Trial?

Interventions

• Pioglitazone

Trial Overview The study tests pioglitazone's ability to reduce muscle fatigue in breast cancer patients by adjusting gene activity in skeletal muscles. Participants will receive either 30 mg or 15 mg of pioglitazone daily in this off-label use case to see if it can alleviate fatigue symptoms.

How Is the Trial Designed?

Group I: Pioglitazone 15mg Dose Active Control 1 Intervention

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.

Group II: Pioglitazone 30mg Dose Active Control 1 Intervention

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.

Group III: No Drug Active Control 1 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.

Pioglitazone is already approved in United States for the following indications:

Approved in United States as Actos for:

• Type 2 diabetes mellitus

Who Is Running the Clinical Trial?

West Virginia University

Lead Sponsor

Trials

192

Recruited

64,700+

Citations

1. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05013255/pioglitazone-therapy-targeting-fatigue-in-breast-cancer

Pioglitazone Therapy Targeting Fatigue in Breast Cancer The goal of this project is to evaluate the therapeutic potential of pioglitazone (PIO) to target underlying mechanisms that promote muscle ...

2. trial.medpath.com trial.medpath.com/clinical-trial/7a56a3865fd456ec/nct05013255-pioglitazone-therapy-breast-cancer

Pioglitazone Therapy Targeting Fatigue in Breast Cancer 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 ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11544806/

Preclinical Multi-Omic Assessment of Pioglitazone in ... Our results showed molecular improvements in muscle tissue, although the drug did not improve muscle fatigue. These findings show that pioglitazone may offer ...

4. withpower.com withpower.com/trial/phase-3-breast-neoplasms-8-2021-0831c

Pioglitazone for Fatigue in Breast Cancer Trial Overview The study tests pioglitazone's ability to reduce muscle fatigue in breast cancer patients by adjusting gene activity in skeletal muscles.

5. researchgate.net researchgate.net/publication/385372511_Preclinical_Multi-Omic_Assessment_of_Pioglitazone_in_Skeletal_Muscles_of_Mice_Implanted_with_Human_HER2neu_Overexpressing_Breast_Cancer_Xenografts

(PDF) Preclinical Multi-Omic Assessment of Pioglitazone in ... Here, we conducted a preclinical trial of pioglitazone in BC-PDOX mice to determine its efficacy in ameliorating BC-induced muscle fatigue, as ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9118720/

Pioglitazone and breast cancer risk in female patients with ... This study suggests a null association between pioglitazone and breast cancer risk in female patients with type 2 diabetes mellitus.

7. clinconnect.io clinconnect.io/trials/NCT05013255

Pioglitazone Therapy Targeting Fatigue in Breast Cancer Fatigue is a common and challenging symptom for cancer patients, and this study aims to understand if pioglitazone can improve energy levels by targeting ...

8. mdpi.com mdpi.com/2072-6694/16/21/3640

Preclinical Multi-Omic Assessment of Pioglitazone in ... Currently, there are no approved treatments for this fatigue. In this study, we tested pioglitazone, an FDA-approved drug, in a mouse model of breast cancer.

9. researchgate.net researchgate.net/publication/24250119_Safety_and_Tolerability_of_Pioglitazone_in_High-Risk_Patients_with_Type_2_Diabetes_An_Overview_of_Data_from_PROactive

Safety and Tolerability of Pioglitazone in High-Risk ... Overall, safety and tolerability was predictable, and adverse events were not treatment limiting. These results suggest that any beneficial ...