search
Back to results

Testosterone Replacement in Male Cancer Survivors With Fatigue and Low Testosterone

Primary Purpose

Hypogonadism, Male, Fatigue Syndrome, Chronic

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Testosterone Undecanoate 750 MG/3 ML Intramuscular Solution [AVEED]
placebo
Sponsored by
Seattle Institute for Biomedical and Clinical Research
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hypogonadism, Male focused on measuring testosterone, hypogonadism, cancer related fatigue

Eligibility Criteria

18 Years - 54 Years (Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria:

  • Cancer survivors who have received chemotherapy and/or radiation therapy for their cancer and are now in remission for at least one year
  • Non-hormone-dependent cancer, including most solid tumors, lymphomas and leukemias
  • Age: 18-54 years
  • Serum testosterone, measured by mass spectrometry (gold standard method), of <348 ng/dl and/or free testosterone <70 pg/ml. The lower limits of the normal range for total testosterone in healthy young men (age 19-40 years), is 348 ng/dL and the lower limits of free testosterone is <70 pg/ml in the Framingham Heart Study sample97. Therefore, young symptomatic men with total testosterone <348 ng/dl could be considered testosterone deficient. As sex hormone binding globulin levels may be elevated in some men with cancer (resulting in elevation in total testosterone level), some of these symptomatic men may still be hypogonadal despite having total testosterone above this cut-off limit. However; their free testosterone levels may still be below the lower limit of normal. Thus, we will also include men with free testosterone <70 pg/mL.
  • Self-reported fatigue. We have selected these symptoms because they are commonly reported in male cancer survivors. Fatigue will be defined as a score on Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) subscale of <40, which best divides cancer patients from the general population with 84% accuracy, and was used as the cut-off for the NIA-funded 50-million-dollar testosterone trial (The T-Trial).
  • Ability and willingness to provide informed consent.

Exclusion Criteria:

  • Men with hormone-dependent cancers (breast, prostate or adenocarcinoma of unknown origin)
  • Men with brain cancer (potential cognitive impairment)
  • Use of anabolic agents (testosterone, dehydroepiandrosterone, growth hormone) within the past 6 months
  • Appetite stimulating agents e.g. megestrol acetate within the past 6 months
  • Systemic glucocorticoids e.g. prednisone 20 mg daily or equivalent doses of other glucocorticoids for more than two weeks in the past 6 months
  • Baseline hematocrit >48%
  • PSA >4 ng/ml in Caucasians; >3 ng/ml in African-Americans; nodule/induration on digital rectal exam
  • Men with 1st order relatives with a history of prostate cancer
  • Uncontrolled congestive heart failure
  • Severe untreated sleep apnea

  • Myocardial infarction, acute coronary syndrome, revascularization surgery, or stroke within 3 months

    o Previous stroke with residual cognitive or functional deficits; Mini-Mental State Examination score <24

  • Serum creatinine >2.5 mg/dL; ALT 3x upper limit of normal
  • Poorly controlled diabetes as defined by hemoglobin A1c >8.5%; Body mass index (BMI) >45 kg/m2
  • Untreated unipolar depression (treated depression with medications or counseling will be allowed
  • Bipolar disorder or schizophrenia

Sites / Locations

  • Brigham and Women's HospitalRecruiting
  • Veterans Affairs Puget Sound Health Care SystemRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Testosterone

Placebo

Arm Description

Testosterone undecanoate injection 750 MG/3 ML

clinical grade saline 0.9% sodium chloride injection

Outcomes

Primary Outcome Measures

Fatigue change
(Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F) questionnaire

Secondary Outcome Measures

Sexual function change
Harbor-UCLA 7-day Sexual Function Questionnaire
Sexual function change
International Index of Erective Function (IIEF) questionnaire
Body composition change
Lean body mass and fat mass (kg) measured by dual energy x-ray absorptiometry (DEXA)
Changes to mood and well-being
Mood and well-being will be assessed by the Positive and Negative Affect Scale (PANAS) affectivity balance scale, which includes 10 questions each for Positive Affect and Negative Affect. Many behavioral scientists consider affectivity as the cleanest window on an individual's wellbeing. The most sensitive indicator of impaired wellbeing has been shown to be affective dysregulation, which is reflected in affectivity balance. The latter incorporates negative affects (e.g., anxiety, depression) as well as positive affects (e.g., joy).
Muscle strength change
Maximal voluntary muscle strength in the lower extremities will be assessed by conducting the leg press exercise by the 1-repetition maximum method and assessing loaded stair climb power.
Sleep quality change
Pittsburgh Sleep Quality Index (PSQI)
Sleep quality change
Insomnia Severity Index (ISI)
Sleep quality change
Actigraphy
Daily physical activity change
Validated triaxial accelerometry (actigraphy)

Full Information

First Posted
July 23, 2019
Last Updated
March 23, 2023
Sponsor
Seattle Institute for Biomedical and Clinical Research
search

1. Study Identification

Unique Protocol Identification Number
NCT04049331
Brief Title
Testosterone Replacement in Male Cancer Survivors With Fatigue and Low Testosterone
Official Title
Improving Patient-Important Outcomes With Testosterone Replacement in Hypogonadal Men With a Prior History of Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 22, 2021 (Actual)
Primary Completion Date
January 30, 2026 (Anticipated)
Study Completion Date
January 30, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Seattle Institute for Biomedical and Clinical Research

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The overall goal of this study is to evaluate the effect of a testosterone drug called Depo-Testosterone (or 'testosterone cypionate'), an FDA-approved drug for improving fatigue, sexual function, quality of life, body composition, muscle strength, and physical activity in young cancer survivors who report fatigue and have low testosterone. Main hypothesis is that Testosterone administration in young male cancer survivors who are in remission for at least 1 year, report cancer-related fatigue and have symptomatic testosterone deficiency will be associated with greater improvements in fatigue scores compared with placebo.
Detailed Description
The overall goal of this proposal is to evaluate the efficacy of testosterone replacement therapy in improving fatigue and other outcomes such as sexual function, quality of life, body composition, muscle strength and physical activity in a double-blind, randomized, placebo-controlled trial in young cancer survivors who report fatigue and have testosterone deficiency. Fatigue is one of the most prevalent and debilitating symptoms in men with cancer affecting 70-100% of patients irrespective of their age. Cancer-related fatigue is experienced by patients not only during active cancer treatment, but is also highly prevalent in cancer survivors who exhibit persistent fatigue months to years after the end of their treatment with the highest prevalence being in recipients of chemotherapy and/or radiation therapy. In addition to fatigue, sexual dysfunction is also highly prevalent in male cancer survivors. Male cancer survivors also have increased fat mass and decreased lean body mass, a phenotype that predisposes them to reduced muscle strength. This phenotype of fatigue, sexual dysfunction and adverse body composition is commonly encountered in non-cancer patient populations with testosterone deficiency, a condition which is also highly prevalent (50-90%) in cancer survivors. Pivotal trials of testosterone replacement therapy in non-cancer patient populations have shown an improvement in fatigue, sexual function and body composition in men randomized to testosterone compared with placebo. However, the efficacy of testosterone replacement therapy on cancer-related fatigue has not been studied.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypogonadism, Male, Fatigue Syndrome, Chronic
Keywords
testosterone, hypogonadism, cancer related fatigue

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
240 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Testosterone
Arm Type
Experimental
Arm Description
Testosterone undecanoate injection 750 MG/3 ML
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
clinical grade saline 0.9% sodium chloride injection
Intervention Type
Drug
Intervention Name(s)
Testosterone Undecanoate 750 MG/3 ML Intramuscular Solution [AVEED]
Other Intervention Name(s)
study drug
Intervention Description
first two doses four weeks apart; following three more doses every ten weeks.
Intervention Type
Other
Intervention Name(s)
placebo
Intervention Description
first two doses four weeks apart; following three more doses every ten weeks.
Primary Outcome Measure Information:
Title
Fatigue change
Description
(Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F) questionnaire
Time Frame
9 months
Secondary Outcome Measure Information:
Title
Sexual function change
Description
Harbor-UCLA 7-day Sexual Function Questionnaire
Time Frame
9 months
Title
Sexual function change
Description
International Index of Erective Function (IIEF) questionnaire
Time Frame
9 months
Title
Body composition change
Description
Lean body mass and fat mass (kg) measured by dual energy x-ray absorptiometry (DEXA)
Time Frame
9 months
Title
Changes to mood and well-being
Description
Mood and well-being will be assessed by the Positive and Negative Affect Scale (PANAS) affectivity balance scale, which includes 10 questions each for Positive Affect and Negative Affect. Many behavioral scientists consider affectivity as the cleanest window on an individual's wellbeing. The most sensitive indicator of impaired wellbeing has been shown to be affective dysregulation, which is reflected in affectivity balance. The latter incorporates negative affects (e.g., anxiety, depression) as well as positive affects (e.g., joy).
Time Frame
9 months
Title
Muscle strength change
Description
Maximal voluntary muscle strength in the lower extremities will be assessed by conducting the leg press exercise by the 1-repetition maximum method and assessing loaded stair climb power.
Time Frame
9 months
Title
Sleep quality change
Description
Pittsburgh Sleep Quality Index (PSQI)
Time Frame
9 months
Title
Sleep quality change
Description
Insomnia Severity Index (ISI)
Time Frame
9 months
Title
Sleep quality change
Description
Actigraphy
Time Frame
9 months
Title
Daily physical activity change
Description
Validated triaxial accelerometry (actigraphy)
Time Frame
9 months

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
54 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Cancer survivors who have received chemotherapy and/or radiation therapy for their cancer and are now in remission for at least one year Non-hormone-dependent cancer, including most solid tumors, lymphomas and leukemias Age: 18-54 years Serum testosterone, measured by mass spectrometry (gold standard method), of <348 ng/dl and/or free testosterone <70 pg/ml. The lower limits of the normal range for total testosterone in healthy young men (age 19-40 years), is 348 ng/dL and the lower limits of free testosterone is <70 pg/ml in the Framingham Heart Study sample97. Therefore, young symptomatic men with total testosterone <348 ng/dl could be considered testosterone deficient. As sex hormone binding globulin levels may be elevated in some men with cancer (resulting in elevation in total testosterone level), some of these symptomatic men may still be hypogonadal despite having total testosterone above this cut-off limit. However; their free testosterone levels may still be below the lower limit of normal. Thus, we will also include men with free testosterone <70 pg/mL. Self-reported fatigue. We have selected these symptoms because they are commonly reported in male cancer survivors. Fatigue will be defined as a score on Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) subscale of <40, which best divides cancer patients from the general population with 84% accuracy, and was used as the cut-off for the NIA-funded 50-million-dollar testosterone trial (The T-Trial). Ability and willingness to provide informed consent. Exclusion Criteria: Men with hormone-dependent cancers (breast, prostate or adenocarcinoma of unknown origin) Men with brain cancer (potential cognitive impairment) Use of anabolic agents (testosterone, dehydroepiandrosterone, growth hormone) within the past 6 months Appetite stimulating agents e.g. megestrol acetate within the past 6 months Systemic glucocorticoids e.g. prednisone 20 mg daily or equivalent doses of other glucocorticoids for more than two weeks in the past 6 months Baseline hematocrit >48% PSA >4 ng/ml in Caucasians; >3 ng/ml in African-Americans; nodule/induration on digital rectal exam Men with 1st order relatives with a history of prostate cancer Uncontrolled congestive heart failure Severe untreated sleep apnea Myocardial infarction, acute coronary syndrome, revascularization surgery, or stroke within 3 months o Previous stroke with residual cognitive or functional deficits; Mini-Mental State Examination score <24 Serum creatinine >2.5 mg/dL; ALT 3x upper limit of normal Poorly controlled diabetes as defined by hemoglobin A1c >8.5%; Body mass index (BMI) >45 kg/m2 Untreated unipolar depression (treated depression with medications or counseling will be allowed Bipolar disorder or schizophrenia
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jose M Garcia, MD, PhD
Phone
206 764 2984
Email
jg77@uw.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jose M Garcia, MD, PhD
Organizational Affiliation
VA Puget Sound Health Care System
Official's Role
Principal Investigator
Facility Information:
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Milena Braga, MD
Phone
617-525-9144
Email
mbraga@bwh.harvard.edu
First Name & Middle Initial & Last Name & Degree
Shehzad Basaria, MD
Facility Name
Veterans Affairs Puget Sound Health Care System
City
Seattle
State/Province
Washington
ZIP/Postal Code
98108
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Gary Miranda, LPN
Phone
206-277-6143
Email
Gary.Miranda@va.gov
First Name & Middle Initial & Last Name & Degree
Lindsey Anderson, PhD
Phone
2062776719
Email
Lindsey.Anderson5@va.gov
First Name & Middle Initial & Last Name & Degree
Jose M Garcia, MD, PhD

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Testosterone Replacement in Male Cancer Survivors With Fatigue and Low Testosterone

We'll reach out to this number within 24 hrs