Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Intramuscular Mechanisms of Androgen Deprivation-related Sarcopenia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03867357
Recruitment Status : Recruiting
First Posted : March 8, 2019
Last Update Posted : March 8, 2019
Sponsor:
Collaborators:
United States Department of Defense
University of Washington
Information provided by (Responsible Party):
Seattle Institute for Biomedical and Clinical Research

Tracking Information
First Submitted Date February 26, 2019
First Posted Date March 8, 2019
Last Update Posted Date March 8, 2019
Actual Study Start Date December 7, 2018
Estimated Primary Completion Date August 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: March 5, 2019)
  • 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).
Original Primary Outcome Measures Same as current
Change History No Changes Posted
Current Secondary Outcome Measures
 (submitted: March 5, 2019)
  • 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
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures
 (submitted: March 5, 2019)
Degree of androgen deprivation [ Time Frame: Baseline to 6 months ]
Total and free testosterone levels in blood draw samples
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title Intramuscular Mechanisms of Androgen Deprivation-related Sarcopenia
Official Title Intramuscular Mechanisms of Androgen Deprivation-related Sarcopenia
Brief Summary

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.

Detailed Description

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
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples Without DNA
Description:
Plasma
Sampling Method Non-Probability Sample
Study Population Male Veteran patients presenting with advanced or metastatic PCa eligible for ADT in the Urology clinic at the Veterans Affairs Puget Sound Health Care System.
Condition
  • Metastatic Prostate Cancer
  • Androgen Deprivation Therapy
Intervention 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
Study Groups/Cohorts Not Provided
Publications * Shanely RA, Zwetsloot KA, Triplett NT, Meaney MP, Farris GE, Nieman DC. Human skeletal muscle biopsy procedures using the modified Bergström technique. J Vis Exp. 2014 Sep 10;(91):51812. doi: 10.3791/51812.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: March 5, 2019)
60
Original Estimated Enrollment Same as current
Estimated Study Completion Date August 31, 2021
Estimated Primary Completion Date August 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • Histologically, cytologically, or image based documented advanced or metastatic PCa initiating ADT with expected continuous treatment for a minimum of 6 months and willing/able to provide informed consent.
  • Willing and able to provide written informed consent prior to screening.

Exclusion Criteria:

  • Liver disease (AST or ALT equal or more than 3x normal levels);
  • Renal failure (creatinine equal or more than 2.5 mg/dL);
  • Untreated thyroid disease, class III-IV CHF, AIDS;
  • Other cancer diagnosed within the past five years other than non-melanoma skin cancer;
  • Severe COPD requiring use of home O2;
  • Chronic, uncontrolled hypertension as judged by the Investigator (i.e., Baseline SBP >150 mm Hg, DBP >90 mm Hg) or a SBP > 150 mm Hg or DBP > 95 mm Hg at the time of screening or baseline;
  • An active, uncontrolled infection or cardiovascular disease including a recent myocardial infarction (MI), cerebrovascular accident (CVA), arrhythmias or unstable angina (< 6 months);
  • Uncontrolled diabetes mellitus (as defined by a HbA1c equal or more than 9%);
  • Underlying muscular or neuromuscular disorder or neurologic deficit contributing to sarcopenia;
  • Enrolled in a clinical trial involving an investigational product or non-approved use of a drug/device or concurrently enrolled in medical research not scientifically or medically compatible with this study;
  • Current use (within one month) of testosterone, high dose steroids (20mg of prednisone/day for more than 1 month), or megestrol treatment for cancer within the previous 3 months;
  • Previous treatment with ADT other than oral anti-androgen at initiation of ADT;
  • Metal implants in the right limbs (non-MRI compatible metal stents, titanium pins/markers, etc.) or implanted cardiac pacemaker or other implanted non-MRI compatible cardiac device (e.g., stent);
  • A history of vascular problems (DVT, etc.)
Sex/Gender
Sexes Eligible for Study: Male
Ages 18 Years to 90 Years   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts
Contact: Jonathan Lee, BS 2062775087 ext 65087 Jonathan.Lee3@va.gov
Contact: Lindsey Anderson, PhD 2062776719 ext 66719 Lindsey.Anderson5@va.gov
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT03867357
Other Study ID Numbers 1653
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement
Plan to Share IPD: No
Responsible Party Seattle Institute for Biomedical and Clinical Research
Study Sponsor Seattle Institute for Biomedical and Clinical Research
Collaborators
  • United States Department of Defense
  • University of Washington
Investigators
Principal Investigator: Jose M Garcia, MD, PhD Veterans Affairs Puget Sound Health Care System, University of Washington
PRS Account Seattle Institute for Biomedical and Clinical Research
Verification Date March 2019