HypogonadismPhase 4NCT02959853
Aromatase Inhibitors and Weight Loss in Severely Obese Hypogonadal Male Veterans (Pilot)
A Phase 4 study testing Anastrazole and weight loss in people with Hypogonadism and Severe Obesity, run by Baylor College of Medicine at 1 site in United States.
Trial summary
After the age of 40, there is a gradual decline in the production of testosterone. Among obese men, the decline in testosterone levels is exacerbated by the suppression of the hypothalamic-pituitary-gonadal axis by hyperestrogenemia. Read more about this study
- Who is it for?
- Ages 35 to 65 years, men only
- Conditions the study is for
- Hypogonadism, Severe Obesity
- What is being tested?
- Anastrazole and weight loss
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 23 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2016to 20 Dec 2018
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 35 to 65 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- severely obese (BMI >= 35) male veterans with hypogonadotropic hypogonadism defined as low total testosterone (lower than 300 ng/dl) between 35-65 years of age
- Luteinizing hormone (LH) lower than 9 U/L
- estradiol above 40 pmol/l
- normal Free T4 (FT4), Thyroid Stimulating Hormone (TSH), prolactin, cortisol, Adrenocorticotropic hormone (ACTH), and Insulin-like growth factor-1 (IGF-1) levels.
- Subjects must be ambulatory, willing and able to provide written informed consent
Who cannot join
- clinical or biochemical evidence of pituitary or hypothalamic disease
- any ongoing illness that, in the opinion of the investigator, could prevent the subject from completing study
- any med known to affect gonadal hormones, steroid hormone-binding globulin or bone metabolism, e.g.,
- androgens
- estrogens
- glucocorticoids
Show all 31Show fewer
- phenytoin
- bisphosphonates
- any medication known to interfere with anastrozole metabolism, e.g. tamoxifen or estrogens
- diseases known to interfere with bone metabolism as
- osteoporosis
- hyperparathyroidism
- untreated hyperthyroidism
- osteomalacia
- chronic liver disease
- renal failure
- hypercortisolism
- malabsorption
- immobilization
- patients with a Total T score lower than -2.0 at Lumbar Spine or Left Femur.
- patients with symptomatic prostate disease, prostate carcinoma, or elevated serum Prostate-specific antigen (PSA) >4 ng/ml or >3 for subjects with a family history of prostate cancer among 1st degree relatives needs urologic evaluation before admission into study
- hematocrit greater than 50%
- untreated severe obstructive sleep apnea
- severe lower urinary tract symptoms with International Prostate Symptom Score (IPSS) above 19
- documented heart failure
- cardiovascular disease
- liver disease
- excessive alcohol or substance abuse
- unstable weight (changes in weight more than ± 2 kg) during the last 3 months
- history of bariatric surgery
- subjects with elevated liver enzymes as alanine transaminase (ALT), aspartate aminotransferase (AST), Alkaline phosphatase (ALP), and bilirubin at greater than twice the upper limit of normal.
Trial locations and contacts
1 site in 1 country.
United States1 site
Michael E. DeBakey Veterans Affairs Medical Center
Houston, Texas, 77030
About this study
After the age of 40, there is a gradual decline in the production of testosterone. Among obese men, the decline in testosterone levels is exacerbated by the suppression of the hypothalamic-pituitary-gonadal axis by hyperestrogenemia. The high expression of aromatase enzyme in the adipose tissue enhances the conversion of androgens into estrogens which in turn exert a negative feedback on the hypothalamus and pituitary, leading to the inhibition of production of gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH) and follicle stimulating hormone (FSH), and as a consequence, of testosterone by the testis resulting in hypogonadotropic hypogonadism (HH). Though bone loss is a well recognized side effect of AI in certain populations, such as women with breast cancer, HH obese men present high levels of circulating estrogens that could potentially prevent them from bone loss, estradiol being the main regulator of the male skeleton. This study is designed to determine if aromatase inhibitors in combination with weight loss, compared to weight loss alone, will have a positive effect on muscle strength, symptoms of hypogonadism, and body composition without negatively impacting bone mineral density and bone quality. Results from this study will help determine if certain groups of obese patients would benefit from therapy with aromatase inhibitors.
Read the detailed description
After the age of 40, testosterone (T) production in men gradually decreases at a rate of 1.6% per year for total and to 2-3% per year for bioavailable T. Because of the age-related increase in sex hormone binding globulin, the magnitude of the decrease in bioavailable T in men is even greater than the decline in total T levels. This reduction in T production in men parallels the age-associated loss of muscle mass that leads to sarcopenia and impairment of function and the age-associated loss of bone mass that leads to osteopenia and fracture risk. Hypogonadism is a condition associated with multiple symptom complex including fatigue, depressed mood, osteoporosis, increased fat mass, loss of libido and reduced muscle strength, all of which deeply affect patient's quality of life. The prevalence of hypogonadismamong obese men ranges between 29.3% to 78.8%, with levels of androgens decreasing proportionately to the degree of obesity. This decline in T levels is exacerbated among obese patients due the suppression of the hypothalamic-pituitary-gonadal axis by hyperestrogenemia. The high expression of aromatase enzyme in the adipose tissue enhances the conversion of androgens into estrogens (E) which in turn exerts a negative feedback on hypothalamus and pituitary, inhibiting the production of gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH) and follicle stimulating hormone (FSH) and, as a consequence, of T by the testis resulting in hypogonadotropic hypogonadism (HH). Considering the high aromatase expression in the adipose tissue, the administration of T among obese men with HH could increase the conversion of the substrate T to estradiol (E2) and fuels the negative feedback on the hypothalamus and pituitary, producing a greater suppression of GnRH and gonadotropins.
Thus, men with obesity induced HH may benefit from other treatment strategies that target the pathophysiology of the disease. Weight loss intervention which improves hormonal and metabolic abnormalities related to obesity may also be considered a logical approach to improve obesity-induced HH.
One possible approach consists of the use of aromatase inhibitors (AI) to stop the conversion of T to E2 thereby interrupting the vicious cycle of E2 inhibition of the hypothalamic-pituitary-gonadal axis and restoring T production to normal levels. Increased T and reduced E2 levels have been reported in men with low levels of T after AI administration, even though very few studies investigated clinical outcomes.
We believe that AI use could promote positive changes on hypogonadal symptoms and body composition in HH severely obese patients, acting at the physiopathology of the disease without necessarily causing bone loss.
- Conditions
- Hypogonadism, Severe Obesity
- Being tested
- Anastrazole, weight loss
- Keywords
- Hypogonadism, Severe obesity
- Medical subject headings
- Hypogonadism, Obesity, Morbid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AnastrazoleDrug
Also called Arimidex
weight lossBehavioural
| Study group | Role | What they receive |
|---|---|---|
| weight loss | Placebo comparator | Patients given counseling on diet and exercise in order to achieve a goal weight loss of 10 percent Receives: Behavioral: weight loss |
| aromatase inhibitor (anastrazole) plus weight loss | Experimental | Patient placed on an aromatase inhibitor anastrazole 1 mg daily plus given counseling on diet and exercise in order to achieve a goal weight loss of 10 percent Receives: Drug: Anastrazole; Behavioral: weight loss |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change in Muscle Strength as Assessed by Knee Extension and Knee Flexion
Muscle strength was assessed using Biodex System 4 Isokinetic Dynamometer (Shirley, NY). Peak torque for isokinetic knee extension and flexion was measured at baseline, 6 months on the right leg. During the testing, participants sat with their hips flexed at 120 degrees, secured with thigh and pelvic straps. Testing was performed at an angular velocity of 60 degrees per second. The best result of 3 maximal voluntary efforts for each knee flexion and extension was used as the measure of absolute strength and reported as peak torque at 60 degrees in Newton-meter (N*m) units.
The higher the measured Newton-meter (N*m), the greater the measured muscle strength.
Measured: baseline and 6 months
Change in Symptoms Score of Hypogonadism
Symptoms of androgen deficiency were measured with 3 validated questionnaires done at baseline, 3 and 6 months.
- The Quantitative Androgen Deficiency in the Aging Male (qADAM) questionnaire uses questions from a scale of 1-5. The final summation yields a total score between 10 (most symptomatic) and 50 (least symptomatic).
- The second questionnaire used was the International Index of Erectile Function (IIEF). Total score ranges from 5 to 25, with 5 being severe erectile dysfunction and 25 being no erectile dysfunction.
- The third questionnaire used was the Impact of Weight on Quality of Life Questionnaire-Lite (IWQOL-lite). Total score ranges from 31 to 155, with 31 being least symptomatic and 155 being the most symptomatic.
Score change at 3 months calculated by: total score at 3 months minus total score at baseline
Score change at 6 months calculated by: total score at 6 months minus total score at baseline
Measured: baseline, 3 and 6 months
Secondary outcomes (4)
Change in Fat Mass (in Kilograms)
change in fat was measured by Dual-energy X-ray absorptiometry (DXA) scan at baseline and 6 months only.
Measured: baseline and 6 months
Change in Visceral Adipose Tissue (in Grams)
Change in absolute visceral adipose tissue as measured by DXA scan, done at baseline and 6 months.
Measured: baseline and 6 months
Percent Change in Bone Mineral Density
Percent change in bone mineral density as measured by DXA scan, done at baseline and 6 months
Measured: baseline and 6 months
Percent Change in Bone Quality
Percent change in bone quality as measured by high resolution peripheral quantitative computed tomography scan (HR-pQCT), at baseline and 6 months
Measured: baseline and 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Nov 2016 (estimated)
- Study startJun 2016
- Primary completion20 Nov 2018
- Study completion20 Dec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HypogonadismStudies of the same condition, open and under way.
- More trials run by Baylor College of MedicineThe sponsor's other registered studies.
- 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
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baylor College of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Rui Chen, Baylor College of Medicine
- Investigators
- Reina Villareal, MD, Principal investigator, Baylor College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02959853
- Sponsor's protocol ID
- H-36912
- Status last verified
- Jan 2020
- First submitted
- 3 Nov 2016
- Last updated
- 30 Jan 2020
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Colleluori G, Chen R, Turin CG, Vigevano F, Qualls C, Johnson B, Mediwala S, Villareal DT, Armamento-Villareal R. Aromatase Inhibitors Plus Weight Loss Improves the Hormonal Profile of Obese Hypogonadal Men Without Causing Major Side Effects. Front Endocrinol (Lausanne). 2020 May 15;11:277. doi: 10.3389/fendo.2020.00277. eCollection 2020.
PubMed 32499757
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Aromatase Inhibitors and Weight Loss in Severely Obese Hypogonadal Male Veterans (Pilot)
- ClinicalTrials.gov ID
- NCT02959853
- Acronym / sponsor ID
- H-36912
- Conditions
- Hypogonadism, Severe Obesity
- Keywords
- Hypogonadism, Severe obesity
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Baylor College of MedicineUniversity, hospital or other
- Study start
- Jun 2016 (actual)
- Primary completion
- 20 Nov 2018 (actual)
- Study completion
- 20 Dec 2018 (actual)
- First posted
- 9 Nov 2016 (estimated)
- Results
- Posted 30 Jan 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
After the age of 40, there is a gradual decline in the production of testosterone. Among obese men, the decline in testosterone levels is exacerbated by the suppression of the hypothalamic-pituitary-gonadal axis by hyperestrogenemia. The high expression of aromatase enzyme in the adipose tissue enhances the conversion of androgens into estrogens which in turn exert a negative feedback on the hypothalamus and pituitary, leading to the inhibition of production of gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH) and follicle stimulating hormone (FSH), and as a consequence, of testosterone by the testis resulting in hypogonadotropic hypogonadism (HH). Though bone loss is a well recognized side effect of AI in certain populations, such as women with breast cancer, HH obese men present high levels of circulating estrogens that could potentially prevent them from bone loss, estradiol being the main regulator of the male skeleton. This study is designed to determine if aromatase inhibitors in combination with weight loss, compared to weight loss alone, will have a positive effect on muscle strength, symptoms of hypogonadism, and body composition without negatively impacting bone mineral density and bone quality. Results from this study will help determine if certain groups of obese patients would benefit from therapy with aromatase inhibitors.
Detailed description
After the age of 40, testosterone (T) production in men gradually decreases at a rate of 1.6% per year for total and to 2-3% per year for bioavailable T. Because of the age-related increase in sex hormone binding globulin, the magnitude of the decrease in bioavailable T in men is even greater than the decline in total T levels. This reduction in T production in men parallels the age-associated loss of muscle mass that leads to sarcopenia and impairment of function and the age-associated loss of bone mass that leads to osteopenia and fracture risk. Hypogonadism is a condition associated with multiple symptom complex including fatigue, depressed mood, osteoporosis, increased fat mass, loss of libido and reduced muscle strength, all of which deeply affect patient's quality of life. The prevalence of hypogonadismamong obese men ranges between 29.3% to 78.8%, with levels of androgens decreasing proportionately to the degree of obesity. This decline in T levels is exacerbated among obese patients due the suppression of the hypothalamic-pituitary-gonadal axis by hyperestrogenemia. The high expression of aromatase enzyme in the adipose tissue enhances the conversion of androgens into estrogens (E) which in turn exerts a negative feedback on hypothalamus and pituitary, inhibiting the production of gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH) and follicle stimulating hormone (FSH) and, as a consequence, of T by the testis resulting in hypogonadotropic hypogonadism (HH). Considering the high aromatase expression in the adipose tissue, the administration of T among obese men with HH could increase the conversion of the substrate T to estradiol (E2) and fuels the negative feedback on the hypothalamus and pituitary, producing a greater suppression of GnRH and gonadotropins.
Thus, men with obesity induced HH may benefit from other treatment strategies that target the pathophysiology of the disease. Weight loss intervention which improves hormonal and metabolic abnormalities related to obesity may also be considered a logical approach to improve obesity-induced HH.
One possible approach consists of the use of aromatase inhibitors (AI) to stop the conversion of T to E2 thereby interrupting the vicious cycle of E2 inhibition of the hypothalamic-pituitary-gonadal axis and restoring T production to normal levels. Increased T and reduced E2 levels have been reported in men with low levels of T after AI administration, even though very few studies investigated clinical outcomes.
We believe that AI use could promote positive changes on hypogonadal symptoms and body composition in HH severely obese patients, acting at the physiopathology of the disease without necessarily causing bone loss.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| weight loss | Placebo comparator | Behavioral: weight lossPatients given counseling on diet and exercise in order to achieve a goal weight loss of 10 percent |
| aromatase inhibitor (anastrazole) plus weight loss | Experimental | Drug: Anastrazole, Behavioral: weight lossPatient placed on an aromatase inhibitor anastrazole 1 mg daily plus given counseling on diet and exercise in order to achieve a goal weight loss of 10 percent |
Who may qualify
- Ages
- 35 to 65 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- severely obese (BMI >= 35) male veterans with hypogonadotropic hypogonadism defined as low total testosterone (lower than 300 ng/dl) between 35-65 years of age
- Luteinizing hormone (LH) lower than 9 U/L
- estradiol above 40 pmol/l
- normal Free T4 (FT4), Thyroid Stimulating Hormone (TSH), prolactin, cortisol, Adrenocorticotropic hormone (ACTH), and Insulin-like growth factor-1 (IGF-1) levels.
- Subjects must be ambulatory, willing and able to provide written informed consent
Key exclusion criteria (31 listed)
- clinical or biochemical evidence of pituitary or hypothalamic disease
- any ongoing illness that, in the opinion of the investigator, could prevent the subject from completing study
- any med known to affect gonadal hormones, steroid hormone-binding globulin or bone metabolism, e.g.,
- diseases known to interfere with bone metabolism as
- patients with symptomatic prostate disease, prostate carcinoma, or elevated serum Prostate-specific antigen (PSA) >4 ng/ml or >3 for subjects with a family history of prostate cancer among 1st degree relatives needs urologic evaluation before admission into study
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 |
|---|---|---|
| AnastrazoleAlso: Arimidex | Drug | aromatase inhibitor (anastrazole) plus weight loss |
| weight loss | Behavioural | aromatase inhibitor (anastrazole) plus weight loss, weight loss |
Primary outcome
Percent Change in Muscle Strength as Assessed by Knee Extension and Knee Flexion
Time frame: baseline and 6 months
Muscle strength was assessed using Biodex System 4 Isokinetic Dynamometer (Shirley, NY). Peak torque for isokinetic knee extension and flexion was measured at baseline, 6 months on the right leg. During the testing, participants sat with their hips flexed at 120 degrees, secured with thigh and pelvic straps. Testing was performed at an angular velocity of 60 degrees per second. The best result of 3 maximal voluntary efforts for each knee flexion and extension was used as the measure of absolute strength and reported as peak torque at 60 degrees in Newton-meter (N*m) units. The higher the measured Newton-meter (N*m), the greater the measured muscle strength.
Change in Symptoms Score of Hypogonadism
Time frame: baseline, 3 and 6 months
Symptoms of androgen deficiency were measured with 3 validated questionnaires done at baseline, 3 and 6 months. 1. The Quantitative Androgen Deficiency in the Aging Male (qADAM) questionnaire uses questions from a scale of 1-5. The final summation yields a total score between 10 (most symptomatic) and 50 (least symptomatic). 2. The second questionnaire used was the International Index of Erectile Function (IIEF). Total score ranges from 5 to 25, with 5 being severe erectile dysfunction and 25 being no erectile dysfunction. 3. The third questionnaire used was the Impact of Weight on Quality of Life Questionnaire-Lite (IWQOL-lite). Total score ranges from 31 to 155, with 31 being least symptomatic and 155 being the most symptomatic. Score change at 3 months calculated by: total score at 3 months minus total score at baseline Score change at 6 months calculated by: total score at 6 months minus total score at baseline
4 secondary outcomes
Change in Fat Mass (in Kilograms)
Time frame: baseline and 6 months
Change in Visceral Adipose Tissue (in Grams)
Time frame: baseline and 6 months
Percent Change in Bone Mineral Density
Time frame: baseline and 6 months
Percent Change in Bone Quality
Time frame: baseline and 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32499757Colleluori G, Chen R, Turin CG, Vigevano F, Qualls C, Johnson B, Mediwala S, Villareal DT, Armamento-Villareal R. Aromatase Inhibitors Plus Weight Loss Improves the Hormonal Profile of Obese Hypogonadal Men Without Causing Major Side Effects. Front Endocrinol (Lausanne). 2020 May 15;11:277. doi: 10.3389/fendo.2020.00277. eCollection 2020.
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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.
Reina Villareal, MD principal investigator
Baylor College of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Anastrazole and weight loss in people with Hypogonadism and Severe Obesity, run by Baylor College of Medicine 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 5 inclusion and 31 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 30 Jan 2020. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Percent Change in Muscle Strength as Assessed by Knee Extension and Knee Flexion (time frame: baseline and 6 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 NCT02959853, 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 30 Jan 2020; AzTrials last refreshed its copy on 8 Nov 2026.