NCT05013255

Pioglitazone Therapy Targeting Fatigue in Breast Cancer

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: West Virginia University · Academic / Other
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

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. 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).

Conditions

• Breast Cancer
• Muscle Fatigue

Interventions

Type	Name	Description
DRUG	Pioglitazone 15mg	PIO 15mg orally once daily for 2 weeks
DRUG	Pioglitazone 30 mg	PIO 30mg orally once daily for 2 weeks

Timeline

• Start date: 2021-12-23
• Primary completion: 2026-12-01
• Completion: 2026-12-01
• First posted: 2021-08-19
• Last updated: 2025-04-08

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study