Intramuscular Mechanisms of Androgen Deprivation-related Sarcopenia
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|ClinicalTrials.gov Identifier: NCT03867357|
Recruitment Status : Recruiting
First Posted : March 8, 2019
Last Update Posted : March 8, 2019
Prostate cancer (PCa) is the most common cancer among men and is even more common in the military and veteran population. For patients with advanced prostate cancer, the most common treatment includes lowering the levels of the hormone testosterone as much as possible. This is called "androgen deprivation therapy" or "ADT". Unfortunately, ADT also causes patients to be fatigued, weak and to loose muscle. This is often referred to as "sarcopenia" and it leads to falls, poor quality of life and higher risk of death. Currently, there is no treatment for sarcopenia because the investigators do not understand the mechanisms that cause it. The mitochondria is the part of the cells responsible for providing energy to muscles but to this date the investigators do not know if it is affected in prostate cancer patients with sarcopenia due to ADT.
The overall goal of this proposal is to establish if the mitochondria is responsible for sarcopenia in patients with prostate cancer receiving ADT. The investigators will measure mitochondrial function, muscle mass and strength, and feelings of fatigue and quality of life in patients with prostate cancer before starting and after 6 months of ADT.
|Condition or disease||Intervention/treatment|
|Metastatic Prostate Cancer Androgen Deprivation Therapy||Drug: GnRH agonist|
Prostate cancer (PCa) is the most common cancer among men. Androgen deprivation therapy (ADT) is the standard treatment for advanced and metastatic PCa and nearly 400,000 men remain on androgen deprivation therapy (ADT) for advanced PCa in the U.S. Unfortunately, ADT also induces a decrease in muscle mass and function, known as sarcopenia, a condition that leads to decreased endurance, increased fatigue, falls, poor health-related quality of life (HR-QOL) and increased mortality. The mechanisms underlying the development of ADT-induced sarcopenia are incompletely understood and remain a significant barrier to the development of therapies for this condition. Mitochondria play an essential role in generating the adenosine triphosphate (ATP) needed for muscle contraction and abnormalities in mitochondria function have been reported in animal models of sarcopenia. The extent to which mitochondrial dysfunction mediates ADT-induced sarcopenia and muscle dysfunction is not known.
The overall goal of this proposal is to establish the role of mitochondrial dysfunction on ADT-induced sarcopenia in patients with PCa. The investigators hypothesize that ADT in men with PCa will induce mitochondrial dysfunction leading to sarcopenia.
Improving scientific understanding of the mechanisms underlying sarcopenia following ADT will enable investigators to develop new treatments and novel biomarkers for this disease. Given that there are no available therapies for sarcopenia, this is clinically very relevant. The near-term impact of this proposal will be to elucidate the extent to which mitochondrial dysfunction mediates the development of sarcopenia in veterans and non-veterans with prostate cancer undergoing ADT, and to evaluate the potential for these measurements at baseline to serve as early predictors of disease. The outcomes that will be directly attributed to the results of the proposed research include baseline and changes in muscle mass and performance, in-vivo and ex-vivo mitochondrial function, and patient reported outcomes (PROs) including fatigue and HR-QOL. The investigators expect that these efforts will have a major impact on the goal of reducing morbidity associated with prostate cancer, and improving HR-QOL by filling the gap in the knowledge of the mechanisms causing ADT-induced sarcopenia in PCa. The mechanisms identified in this grant will be the target of future interventional clinical trials.
The proposed project will address one of the PCRP overarching challenges and focus areas: "Survivorship including psychosocial impact on the patient". If the investigators prove the hypothesis that mitochondrial dysfunction plays a significant role in the development of sarcopenia, fatigue and poor HR-QOL in veterans and non-veterans with prostate cancer, the multidisciplinary team that has been assembled will build on these findings and test interventions currently undergoing clinical development to target mitochondria dysfunction in this population.
|Study Type :||Observational|
|Estimated Enrollment :||60 participants|
|Official Title:||Intramuscular Mechanisms of Androgen Deprivation-related Sarcopenia|
|Actual Study Start Date :||December 7, 2018|
|Estimated Primary Completion Date :||August 31, 2021|
|Estimated Study Completion Date :||August 31, 2021|
- Drug: GnRH agonist
Zoladex is a gonadotropin-releasing hormone agonist, or GnRH-A. It is an implant that is injected under the skin (subcutaneously). The implant gradually dissolves and releases the drug over the time between injections. There are two dosages of Zoladex: Zoladex 10.8 mg, which is injected once every 3 months, and Zoladex 3.6 mg, which is injected once a month.Other Name: Zoladex, Goserelin
- Lean body mass (LBM) change [ Time Frame: Baseline to 3 months ]Changes in LBM (kg) measured by X-ray densitometry (DEXA).
- Lean body mass (LBM) change [ Time Frame: Baseline to 6 months ]Changes in LBM (kg) measured by X-ray densitometry (DEXA).
- Body composition change [ Time Frame: Baseline to 6 months ]Lean body mass and fat mass (kg) measured by dual energy x-ray absorptiometry (DEXA)
- Muscle strength change [ Time Frame: Baseline to 6 months ]Hand grip strength (kg)
- Muscle strength change [ Time Frame: Baseline to 6 months ]Stair climb power (seconds)
- Aerobic capacity change [ Time Frame: Baseline to 6 months ]VO2 max
- Daily physical activity change [ Time Frame: Baseline to 6 months ]Actigraphy
- Skeletal muscle mitochondrial function (in vivo) [ Time Frame: Baseline to 6 months ]Magnetic resonance spectroscopy (MRS)
- Skeletal muscle mitochondrial function (ex vivo) [ Time Frame: Baseline to 6 months ]Oxygen consumption rate (OCR)
- Quality-of-life change [ Time Frame: Baseline to 6 months ]EORTC Quality of Life Questionnaire (EORTC QLQ-C30)
- Quality-of-life change [ Time Frame: Baseline to 6 months ]Expanded Prostate Cancer Index Composite (EPIC) questionnaire
- Quality-of-life change [ Time Frame: Baseline to 6 months ]Functional Assessment of Cancer Therapy-Prostate questionnaire
- Degree of androgen deprivation [ Time Frame: Baseline to 6 months ]Total and free testosterone levels in blood draw samples
Biospecimen Retention: Samples Without DNA
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03867357
|Contact: Jonathan Lee, BS||2062775087 ext 65087||Jonathan.Lee3@va.gov|
|Contact: Lindsey Anderson, PhD||2062776719 ext 66719||Lindsey.Anderson5@va.gov|
|United States, Washington|
|Veterans Affairs Puget Sound Health Care System||Recruiting|
|Seattle, Washington, United States, 98108|
|Contact: Jonathan Lee, BS 206-277-5087 ext 65087 Jonathan.Lee3@va.gov|
|Contact: Lindsey Anderson, PhD 2062776719 ext 66719 Lindsey.Anderson5@va.gov|
|Principal Investigator: Jose M Garcia, MD, PhD|
|Principal Investigator:||Jose M Garcia, MD, PhD||Veterans Affairs Puget Sound Health Care System, University of Washington|