Metastatic Prostate CancerNCT03867357
Intramuscular Mechanisms of Androgen Deprivation-related Sarcopenia
An observational study of Metastatic Prostate Cancer and Androgen Deprivation Therapy, run by Seattle Institute for Biomedical and Clinical Research at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 90 years, men only
- Conditions the study is for
- Metastatic Prostate Cancer, Androgen Deprivation Therapy
- What is being tested?
- GnRH agonist
- Type of treatment
- Injection or infusion
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Dec 2018to 1 Sep 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- Men only
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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.
Who cannot join
- 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;
Show all 14Show fewer
- 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.)
Trial locations and contacts
1 site in 1 country.
United States1 site
Veterans Affairs Puget Sound Health Care System
Seattle, Washington, 98108
About this study
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.
Read the 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.
- Being tested
- GnRH agonist
- Keywords
- Androgen deprivation therapy, Prostate cancer, Sarcopenia
- Medical subject headings
- Prostatic Neoplasms, Sarcopenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GnRH agonistDrug
Also called Zoladex, Goserelin
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.
What is being measured
The primary outcome is the main question the study is designed to answer.
Lean body mass (LBM) change
Changes in LBM (kg) measured by X-ray densitometry (DEXA).
Measured: Baseline to 3 months
Lean body mass (LBM) change
Changes in LBM (kg) measured by X-ray densitometry (DEXA).
Measured: Baseline to 6 months
Secondary outcomes (11)
Body composition change
Lean body mass and fat mass (kg) measured by dual energy x-ray absorptiometry (DEXA)
Measured: Baseline to 6 months
Muscle strength change
Hand grip strength (kg)
Measured: Baseline to 6 months
Muscle strength change
Stair climb power (seconds)
Measured: Baseline to 6 months
Muscle thickness change
Changes in muscle thickness by Ultrasound
Measured: Baseline to 6 months
Aerobic capacity change
VO2 max
Measured: Baseline to 6 months
Daily physical activity change
Actigraphy
Measured: Baseline to 6 months
Skeletal muscle mitochondrial function (in vivo)
Magnetic resonance spectroscopy (MRS)
Measured: Baseline to 6 months
Skeletal muscle mitochondrial function (ex vivo)
Oxygen consumption rate (OCR)
Measured: Baseline to 6 months
Quality-of-life change
EORTC Quality of Life Questionnaire (EORTC QLQ-C30)
Measured: Baseline to 6 months
Quality-of-life change
Expanded Prostate Cancer Index Composite (EPIC) questionnaire
Measured: Baseline to 6 months
Quality-of-life change
Functional Assessment of Cancer Therapy-Prostate questionnaire
Measured: Baseline to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Mar 2019
- Study start7 Dec 2018
- Primary completion1 Sep 2023
- Study completion1 Sep 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic Prostate CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Seattle Institute for Biomedical and Clinical Research
- Sponsor type
- University, hospital or other
- Collaborators
- United States Department of Defense, University of Washington
- Responsible party
- Sponsor
- Investigators
- Jose M Garcia, MD, PhD, Principal investigator, Veterans Affairs Puget Sound Health Care System, University of Washington
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03867357
- Sponsor's protocol ID
- 1653
- Status last verified
- Sep 2024
- First submitted
- 26 Feb 2019
- Last updated
- 4 Sep 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 25285722
Study at a glance
From the registry record, last updated by the sponsor on 4 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intramuscular Mechanisms of Androgen Deprivation-related Sarcopenia
- ClinicalTrials.gov ID
- NCT03867357
- Acronym / sponsor ID
- 1653
- Keywords
- Androgen deprivation therapy, Prostate cancer, Sarcopenia
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Seattle Institute for Biomedical and Clinical ResearchUniversity, hospital or other
- Collaborators
- United States Department of Defense, University of Washington
- Study start
- 7 Dec 2018 (actual)
- Primary completion
- 1 Sep 2023 (actual)
- Study completion
- 1 Sep 2023 (actual)
- First posted
- 8 Mar 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 90 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (14 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GnRH agonistAlso: Zoladex, GoserelinZoladex 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. | Drug | – |
Primary outcome
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).
11 secondary outcomes
Body composition change
Time frame: Baseline to 6 months
Muscle strength change
Time frame: Baseline to 6 months
Muscle strength change
Time frame: Baseline to 6 months
Muscle thickness change
Time frame: Baseline to 6 months
Aerobic capacity change
Time frame: Baseline to 6 months
Daily physical activity change
Time frame: Baseline to 6 months
Skeletal muscle mitochondrial function (in vivo)
Time frame: Baseline to 6 months
Skeletal muscle mitochondrial function (ex vivo)
Time frame: Baseline to 6 months
Quality-of-life change
Time frame: Baseline to 6 months
Quality-of-life change
Time frame: Baseline to 6 months
Quality-of-life change
Time frame: Baseline to 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Sep 2024.
- Background: PubMed 25285722Shanely 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jose M Garcia, MD, PhD principal investigator
Veterans Affairs Puget Sound Health Care System, University of Washington
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Metastatic Prostate Cancer and Androgen Deprivation Therapy, run by Seattle Institute for Biomedical and Clinical Research at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Lean body mass (LBM) change (time frame: Baseline to 3 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03867357, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Sep 2024.