Effects of Aromatase Inhibitor Therapy on Muscle Function

NCT03581552 | Completed DMC

• 1 other identifier: IUSCC-0647
• Study Type: observational
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

This is a pilot study designed to examine changes in muscle function after Aromatase Inhibitor (AI) therapy, at both the molecular and clinical level.

Conditions

Breast Cancer; Breast Cancer Female

Keywords

Post Menopausal; ER positive; Aromatase Inhibitor Therapy; Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Changes in calstabin1 binding to RyR1 channels in skeletal muscle

  Changes in calstabin1 binding to RyR1 channels in skeletal muscle of breast cancer patients pre and post exposure to adjuvant aromatase inhibitor therapy

  through day 168 of aromatase inhibitor therapy

Secondary Outcomes (6)

• Changes in ryanodine receptor/calcium release channel (RyR1) oxidation in skeletal muscle

  through day 168 of aromatase inhibitor therapy

• Relationship between changes in RyR1 biochemistry and measures of muscle function

  through day 168 of aromatase inhibitor therapy

• Relationship between markers of bone turnover and changes in RyR1 biochemistry

  through day 168 of aromatase inhibitor therapy

• Relationship between markers of bone turnover and changes in muscle function

  through day 168 of aromatase inhibitor therapy

• Characterize the timing of development of muscle dysfunction following initiation of aromatase inhibitor therapy

  through day 168 of aromatase inhibitor therapy

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Post menopausal women with non metastatic breast cancer planning to initiate aromatase inhibitor therapy at the IU Simon Cancer Center oncology clinic.

You may qualify if:

• Age ≥ 18 years
• Post-menopausal
• Diagnosis of ductal carcinoma in situ (DCIS) or stage I, II, or III ER positive breast cancer
• Plan to initiate an AI per treating physician.
• Completion of all primary therapy for breast cancer, including surgery, radiation, and chemotherapy (should be completed 14 days or more prior to obtaining the baseline muscle biopsy). Ongoing HER2 targeted therapy with trastuzumab and/or pertuzumab is allowed. Ongoing neratinib therapy is not allowed.
• Body weight less than 350 lbs., as dictated by the weight limit for DXA (dual energy x-ray absorptiometry) scanner
• Must be willing to undergo muscle biopsy at baseline and after 24 weeks of AI therapy
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 at the time of study enrollment
• Informed consent and authorization of the release of health information must be obtained according to institutional guidelines

You may not qualify if:

• Unwilling to co-enroll into the FIT core study
• Diagnosis of severe osteopenia or osteoporosis, defined as a bone mineral density of ≥ 2.0 standard deviations below the young adult female reference mean (T score)
• Diagnosis of other disorder affecting bone function or turnover, such as Paget's disease, renal osteodystrophy, parathyroid disorders, or vitamin D deficiency/osteomalacia
• Prior history of non-traumatic, fragility bone fracture
• Any muscle or neuromuscular disorder affecting muscle function, such as muscular dystrophy, myositis, or amyotrophic lateral sclerosis
• Any condition precluding power protocol participation (i.e. exertion on a stationary bicycle), including: New York Heart Association (NYHA) class III or IV congestive heart failure, uncontrolled angina, myocardial infarction in the prior 12 months, orthopedic surgery in the previous 6 months or plans for orthopedic surgery during the study period, chronic uncontrolled pulmonary conditions such as uncontrolled asthma (symptoms \> 2 days/week) or dyspnea requiring oxygen, symptomatic peripheral vascular disease, or any other comorbidity that would interfere with the ability to complete and comply with the protocol in the opinion of the investigator
• Need for daily anticoagulation use
• Allergy to local anesthetic
• Locally recurrent or metastatic breast cancer a. History of prior treated malignancies, other than breast cancer, that are now stable, are in remission, and do not require active therapy, are acceptable.

Sponsors & Collaborators

• Tarah J Ballinger, MD: lead

Study Sites (1)

IU Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Serum blood samples will be collected to measure markers of bone turnover and to perform a serum TGF-β assay. Samples will be collected at baseline and within 14 days of day 168 of aromatase inhibitor (AI) treatment Skeletal muscle tissue will be collected and used to compare relative calstabin1 to RyR1 and RyR1 oxidation before and after exposure to aromatase inhibitor (AI) treatment. One sample will be stored for future research relating to aromatase inhibitor-induced muscle weakness including proteomic research. Four core needle samples will be taken from the quadriceps muscle at baseline and within 14 days of day 168 of AI treatment.

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Tarah Ballinger, MD

  Indiana University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Clinical Medicine

Study Record Dates

• First Submitted: June 4, 2018
• First Posted: July 10, 2018
• Study Start: July 26, 2018
• Primary Completion: February 7, 2020
• Study Completion: February 7, 2020
• Last Updated: May 10, 2021

Record last verified: 2021-05

Locations

US (1)