Androgen Deprivation Therapy Muscle Protein Metabolism and Blood Glucose

NCT03440879 | Terminated DMC

• 1 other identifier: PROST100
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

Prostate cancer (PCa) patients receiving androgen deprivation therapy (ADT) (e.g., Zoladex), experience troublesome side effects during and after treatment (e.g., loss of lean body mass (LBM) and increased fat mass). Although the negative effects of ADT on muscle mass are well documented, the cellular effects of ADT on muscle tissue are still largely unknown, and studies investigating the mechanisms are highly warranted. Furthermore, understanding the cellular mechanisms through which ADT negatively influences muscle mass and glucose metabolism is important so that appropriate measures can be taken to counteract muscle wasting and comorbidities during ADT. Thus, PCa patients on ADT (Zoladex), along with non-ADT treated PCa patients serving as controls, will be invited to participate in this study, that aims to investigate the influence of ADT on the basal muscle protein turnover, as well as the responses to strength training. Secondary aims are to investigate between-group differences in blood glucose and insulin responses following a meal).

Conditions

Prostate Cancer; Resistance Exercise; Androgen Deprivation Therapy

Outcome Measures

Primary Outcomes (1)

• Muscle protein synthesis rate

  The protein synthesis rate will be calculated based on the increased enrichment of deuterium, which will be ingested the week prior to the acute day, in muscle protein isolated from muscle biopsies. Deuterium enrichment is assessed by mass spectrometry.

  The muscle biopsy will be collected two hours after the last exercise session.

Secondary Outcomes (4)

• Muscle cell signalling

  Muscle biopsies will be collected on the Acute day. Muscle biopsies obtained 3.5 (baseline biopsy) and 1 hours (post meal) prior to the last exercise session, and 2 hours (post exercise) after the last exercise session will be used

• Plasma insulin levels

  A fasted blood sample will be collected first thing in the morning at the Acute day. Then again at 15, 30, 45, 60, 75, 90, 105, and 120 minutes post meal and post exercise.

• Plasma glucose levels

  A fasted blood sample will be collected first thing in the morning at the Acute day. Then again at 15, 30, 45, 60, 75, 90, 105, and 120 minutes post meal and post exercise.

• Ribosomal RNA

  Muscle biopsies will be obtained at the Acute day. Muscle biopsies for ribosomal RNA analysis will be obtained 3.5 hours prior to the last exercise session (baseline) and 2 hours post the last exercise session (post exercise)

Other Outcomes (8)

• Single muscle fiber myonuclear domain

  Muscle biopsies will be obtained at the Acute day. For the single fiber analysis, only baseline biopsies obtained 3.5 hours prior to the last exercise session will be used.

• Single muscle fiber power analysis

  Muscle biopsies will be obtained at the Acute day. For the single fiber analysis, only baseline biopsies obtained 3.5 hours prior to the last exercise session will be used.

• Single muscle fiber stiffness

  Muscle biopsies will be obtained at the Acute day. For the single fiber analysis, only baseline biopsies obtained 3.5 hours prior to the last exercise session will be used.

Study Arms (2)

ADT group

EXPERIMENTAL

Prostate cancer patients currently receiving androgen deprivation therapy (Zoladex)

Drug: Zoladex

No-ADT group

NO INTERVENTION

Prostate cancer patients without any history of receiving any form of androgen deprivation therapy

Interventions

Zoladex DRUG

Patients currently treated with Zoladex

Also known as: Androgen deprivation therapy

ADT group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All of the following conditions must apply to the prospective patient at screening prior to participation:
• Histologically verified prostate cancer, and either currently on Zoladex or without any current or no past usage of any ADT
• Between 18 and 75 years of age
• Capable of reading and understanding Norwegian, and able to provide informed consent
• Treating oncologist/ study medical doctor´s (KMR) approval for participation
• Signed informed consent must be obtained and documented according to Good Clinical Practice (GCP), and national/local regulations.

You may not qualify if:

• Patients will be excluded from the study if they meet any of the following criteria:
• Routine resistance training (\>1 weekly session, last six months)
• Treated with Warfarin, or if seponation of acetylsalicylic acid is not recommended
• Conditions where heavy resistance exercise is contraindicated:
• Unregulated hypertension
• Unstable angina pectoris
• Recent myocardial infarction (\<1 year)
• Cardiac arrhythmia
• Chronic obstructive pulmonary disease
• Severe asthma
• Recent stroke (\<1 year)
• Epilepsy
• Insulin-dependent diabetes mellitus
• Unstable bone lesions with increased risk of fractures
• Conditions where patients ability to complete the training sessions is challenged:

Sponsors & Collaborators

• Norwegian School of Sport Sciences: lead
• University Hospital, Akershus: collaborator
• Oslo University Hospital: collaborator
• Rigshospitalet, Denmark: collaborator
• University of Copenhagen: collaborator
• King's College London: collaborator

Study Sites (1)

Norwegian School of Sport Sciences

Oslo, 0806, Norway

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Goserelin; Androgen Antagonists

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Gonadotropin-Releasing Hormone; 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; Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Truls Raastad, Professor

  Norwegian School of Sport Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: February 1, 2018
• First Posted: February 22, 2018
• Study Start: September 21, 2018
• Primary Completion: March 2, 2023
• Study Completion: March 2, 2023
• Last Updated: March 27, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

NO (1)