Aromatase Inhibitors and Weight Loss in Severely Obese Hypogonadal Male Veterans (Pilot)

NCT02959853 | Completed Phase 4 Results

• 1 other identifier: H-36912
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Hypogonadism; Severe Obesity

Keywords

Hypogonadism; Severe obesity

Outcome Measures

Primary Outcomes (2)

• 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.

  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. 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

  baseline, 3 and 6 months

Secondary Outcomes (4)

• Change in Fat Mass (in Kilograms)

  baseline and 6 months

• Change in Visceral Adipose Tissue (in Grams)

  baseline and 6 months

• Percent Change in Bone Mineral Density

  baseline and 6 months

• Percent Change in Bone Quality

  baseline and 6 months

Study Arms (2)

weight loss

PLACEBO COMPARATOR

Patients given counseling on diet and exercise in order to achieve a goal weight loss of 10 percent

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

Drug: Anastrazole; Behavioral: weight loss

Interventions

Anastrazole DRUG

Also known as: Arimidex

aromatase inhibitor (anastrazole) plus weight loss

weight loss BEHAVIORAL

aromatase inhibitor (anastrazole) plus weight loss; weight loss

Eligibility Criteria

• Age: 35 Years - 65 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Baylor College of Medicine: lead

Study Sites (1)

Michael E. DeBakey Veterans Affairs Medical Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• 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.

  PMID: 32499757 DERIVED

MeSH Terms

Conditions

Hypogonadism; Obesity, Morbid

Interventions

Anastrozole

Condition Hierarchy (Ancestors)

Gonadal Disorders; Endocrine System Diseases; Obesity; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Rui Chen
• Organization: Baylor College of Medicine

rui.chen2@bcm.edu

812-239-1855

Study Officials

• Reina Villareal, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 3, 2016
• First Posted: November 9, 2016
• Study Start: June 1, 2016
• Primary Completion: November 20, 2018
• Study Completion: December 20, 2018
• Last Updated: January 30, 2020
• Results First Posted: January 30, 2020

Record last verified: 2020-01

Locations

US (1)