Influence of Aromatase Inhibition on Hepatic- and Cardiac Function in Severe Obese Men (HEPAROB)

Influence of the Aromatase Inhibitor Letrozole on Heart and Liver Function in Obese Men

It seems plausible that increased aromatase activity in obese men, as a result of a larger fat mass, is responsible for decreased levels of testosterone. Therefore aromatase inhibition increases testosterone levels, which may affect hepatic and cardiac function.

In this intervention study two groups of hypogonadal obese men are compared. Group A is treated with Letrozole 2.5 mg (aromatase inhibitor) once every two days during four months; a group with normal testosterone and low oestrogen concentrations. Group B is treated with placebo once every two days during four months; this group will retain low testosterone - and high oestrogenic concentrations.

The primary objective of the study is to evaluate effects of changed sex steroids in obese men on hepatic and cardiac function.

Study Overview

• Status: Completed
• Conditions: Obesity
• Intervention / Treatment: Drug: Letrozole; Drug: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belgium
  • Ghent, Belgium, 9000
    • Ghent University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 58 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Obese male subjects
• Planned for gastric bypass (BMI > 30 kg/m²)
• low testosterone levels
• age between 20 and 65

Exclusion Criteria:

• Primary hypogonadism or secondary hypogonadism due to genetic causes (Kallman syndrome etc.), tumours, infiltrative diseases, infections, pituitary apoplexy, trauma, critical illness, chronic systemic illness or intentional.
• Treatment with corticoids, opiates (on a daily basis), androgen- or estrogen analogs or CYP2A6 substrates (Dexmedetomidine, Ifosfamide, Methoxsalen, Miconazole, Tranylcypromine).
• Impaired renal function defined as serum-creatine > 1.5 mg/dL
• Clinically significant active cardiovascular disease including history of myocardial infarction within the past 6 months and/or heart failure (NYHA class III or IV) at the discretion of the investigator
• Cancer or any clinically significant disease or disorder, which in the investigator's opinion could interfere with the results of the trial
• Palpable prostate nodule or induration, Prostate-specific antigen (PSA) > 3 ng/mL, prostatism, untreated sleep apnea syndrome, erythrocytosis (hematocrit > 50%) or hyperviscosity. (cfr. Endocrine Society Clinical Practice Guideline by Bhasin S et al.)
• Known or suspected abuse of alcohol or narcotics

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo comparator	Drug: Placebo; One placebo capsule every two days during four months
Experimental: Letrozole	Drug: Letrozole; One Letrozole 2.5 mg capsule every two days during four months; Other Names: Femara

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
cardiac function parameters	heart function will be measured by echocardiography.	after 4 months intervention
Hepatic function parameters	Baseline sex steroids will be measured by Liquid chromatography-mass spectrometry (LC-MS/MS) in fasting blood samples, before 10:00 am. Liver function will be analysed by a Nuclear Magnetic Resonance (NMR) recording	before intervention
Hepatic function parameters	Baseline sex steroids will be measured by Liquid chromatography-mass spectrometry (LC-MS/MS) in fasting blood samples, before 10:00 am. Liver function will be analysed by a Nuclear Magnetic Resonance (NMR) recording	after 4 months intervention
cardiac function parameters	heart function will be measured by echocardiography.	before intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
glucose metabolism	Glucose metabolism will be estimated by an oral glucose tolerance test (OGTT).	Before four months intervention.
weight		Before intervention.
weight		after four months intervention.
glucose metabolism	Glucose metabolism will be estimated by an oral glucose tolerance test (OGTT).	Before intervention.

Collaborators and Investigators

• Sponsor: University Hospital, Ghent
• Investigators: Principal Investigator: Johannes Ruige, MD, PhD, University Hospital, Ghent

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: March 17, 2014
• First Submitted That Met QC Criteria: March 24, 2014
• First Posted (Estimate): March 27, 2014

Study Record Updates

• Last Update Posted (Actual): January 24, 2022
• Last Update Submitted That Met QC Criteria: January 21, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: with disturbed glucose metabolism; without disturbed glucose metabolism
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Letrozole
• Other Study ID Numbers: EC/2013/912; 2013-002964-22 (EudraCT Number)