Intramuscular Mechanisms of Androgen Deprivation-related Sarcopenia

NCT03867357 | Completed DMC FDA Drug

• 1 other identifier: 1653
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Metastatic Prostate Cancer; Androgen Deprivation Therapy

Keywords

Androgen deprivation therapy; Prostate cancer; Sarcopenia

Outcome Measures

Primary Outcomes (2)

• Lean body mass (LBM) change

  Changes in LBM (kg) measured by X-ray densitometry (DEXA).

  Baseline to 3 months

• Lean body mass (LBM) change

  Changes in LBM (kg) measured by X-ray densitometry (DEXA).

  Baseline to 6 months

Secondary Outcomes (11)

• Body composition change

  Baseline to 6 months

• Muscle strength change

  Baseline to 6 months

• Muscle strength change

  Baseline to 6 months

• Muscle thickness change

  Baseline to 6 months

• Aerobic capacity change

  Baseline to 6 months

Other Outcomes (1)

• Degree of androgen deprivation

  Baseline to 6 months

Interventions

GnRH agonist DRUG

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.

Also known as: Zoladex, Goserelin

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.

You may not qualify if:

• 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.)

Sponsors & Collaborators

• Seattle Institute for Biomedical and Clinical Research: lead
• United States Department of Defense: collaborator
• University of Washington: collaborator

Study Sites (1)

Veterans Affairs Puget Sound Health Care System

Seattle, Washington, 98108, United States

Location

Related Publications (1)

• Shanely RA, Zwetsloot KA, Triplett NT, Meaney MP, Farris GE, Nieman DC. Human skeletal muscle biopsy procedures using the modified Bergstrom technique. J Vis Exp. 2014 Sep 10;(91):51812. doi: 10.3791/51812.

  PMID: 25285722 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Plasma, muscle samples

MeSH Terms

Conditions

Prostatic Neoplasms; Sarcopenia

Interventions

Gonadotropin-Releasing Hormone; Goserelin

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Muscular Atrophy; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Study Officials

• Jose M Garcia, MD, PhD

  Veterans Affairs Puget Sound Health Care System, University of Washington

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 26, 2019
• First Posted: March 8, 2019
• Study Start: December 7, 2018
• Primary Completion: September 1, 2023
• Study Completion: September 1, 2023
• Last Updated: September 4, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)