Assessment of Changes in Metabolic Activity in Liver & Skeletal Muscle in Patients Suffering From Acromegaly

• Conditions: Acromegaly
• Interventions: Other: 1H/31P Magnetic Resonance Spectroscopy; Other: oral glucose tolerance testing; Other: Thyroid sonography

• Registration Number: NCT02115906
• Lead Sponsor: Medical University of Vienna

Brief Summary

Growth hormone (GH) plays a pivotal role in the regulation of body composition including ectopic lipid deposition in insulin sensitive organs like liver and skeletal muscle. Recent evidence indicates that the GH-IGF1 axis affects body composition via regulating mitochondrial oxidation capacity.

Thus, excessive GH secretion by a pituitary adenoma (Acromegaly) might be accompanied by increased mitochondrial activity leading to inappropriately low intracellular lipid depots, especially in metabolically active tissue like liver and skeletal muscle.

This study aims to assess metabolic activity and intracellular lipid content in skeletal muscle and liver in patients suffering from acromegaly compared to controls by 31P/1H Magnetic resonance spectroscopy before and in follow up examinations 3, 6 and 12 months after initiation of GH lowering treatments including surgery, somatostatinanalogs or pegvisomant, as well as oral glucose tolerance tests at each examination to assess treatment responses and calculate validated parameters for insulin sensitivity and resistance.

Detailed Description

Background: Growth hormone (GH) plays a pivotal role in the regulation of body composition including ectopic lipid deposition in insulin sensitive organs like liver and skeletal muscle. Direct inhibition of growth hormone action by a receptor antagonist has been shown to induce hepatic steatosis and growth hormone replacement decreases liver fat content in obese humans. Of note, recent evidence indicates that the GH-IGF1 axis affects body composition via regulating mitochondrial oxidation capacity.

Hypothesis: Direct and/or indirect effects of GH on mitochondrial function might mediate the changes in body composition and lipid deposition. Thus, excessive GH secretion by a pituitary adenoma (Acromegaly) might be accompanied by increased mitochondrial activity leading to inappropriately low intracellular lipid depots, especially in metabolically active tissue like liver and skeletal muscle.

Aim: Assessment of metabolic activity and intracellular lipid content in skeletal muscle and liver in patients suffering from acromegaly compared to controls.

Methods: Non-interventional study:

* 31P/1H Magnetic resonance spectroscopy before and in follow up examinations 3, 6 and 12 months after initiation of GH lowering treatments including surgery, somatostatinanalogs or pegvisomant.

* oral glucose tolerance tests at each examination to assess treatment responses and calculate validated parameters for insulin sensitivity and resistance.

Study Timeline

• Study First Submitted: 2014-04-11
• Study First Submitted QC: 2014-04-15
• Study First Posted: 2014-04-16
• Study Start: 2014-08
• Status Verified: 2016-09
• Last Update Submitted: 2016-09-26
• Last Update Posted: 2016-09-27
• Primary Completion: 2017-05
• Study Completion: 2018-05

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

• age between 18-75 years

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Exclusion Criteria

• (known) overt diabetes mellitus
• known coronary artery disease (history of myocardial infarction or angina pectoris)
• acute or chronic (inflammatory, metabolic [hyperlipidemia, arterial hypertension, thyroid disorder]) disease (healthy controls)
• intake of medication potentially affecting glucose or lipid metabolism
• metal devices or other magnetic material in or on the subjects body which will be hazardous for NMR investigation [heart pacemaker, brain (aneurysm) clip, nerve stimulators, electrodes, ear implants, post coronary by-pass graft (epicardial pace wires), penile implants, colored contact lenses, patch to deliver medications through the skin, coiled spring intrauterine device, vascular filter for blood clots, orthodontic braces, shunt- spinal or ventricular, any metal implants (rods, joints, plates, pins, screws, nails, or clips without MR-authorization), embolization coil, or any metal fragments or shrapnel in the body].
• tendency toward claustrophobia
• severe liver disorders (plasma transaminases elevated > 3fold)
• any acute inflammatory disease within 2 weeks prior the study
• pregnancy
• nursing
• clinically relevant anemia

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Acromegalic patients	1H/31P Magnetic Resonance Spectroscopy	Acromegalic patients before and after initiation of individual therapy will be investigated by 1H/31P magnetic resonance spectroscopy, thyroid sonography and oral glucose tolerance testing
Healthy control subjects	1H/31P Magnetic Resonance Spectroscopy	Age and Body mass index matched control subjects will be investigated by 1H/31P magnetic resonance spectroscopy and oral glucose tolerance testing
Healthy control subjects	oral glucose tolerance testing	Age and Body mass index matched control subjects will be investigated by 1H/31P magnetic resonance spectroscopy and oral glucose tolerance testing
Acromegalic patients	Thyroid sonography	Acromegalic patients before and after initiation of individual therapy will be investigated by 1H/31P magnetic resonance spectroscopy, thyroid sonography and oral glucose tolerance testing
Acromegalic patients	oral glucose tolerance testing	Acromegalic patients before and after initiation of individual therapy will be investigated by 1H/31P magnetic resonance spectroscopy, thyroid sonography and oral glucose tolerance testing

Primary Outcome Measures

Name	Time	Method
Changes in hepatic energy metabolism	before & 3,6,9, and 12 months after initiation of therapy	The 31P-MRS examinations will be performed in a 7 T MR system (Siemens Healthcare, Erlangen, Germany) using a double-tuned (31P/1H) surface coil (Rapid Biomedical Ltd, Rimpar, Germany), with a diameter of 10 cm.

Secondary Outcome Measures

Name	Time	Method
Changes in hepatic lipid content	before, as well as 3,6,9 &12 months after initiation of therapy	Hepatic lipid content will be assessed using localized single voxel 1H MRS as published by our study group. STEAM sequence (VOI= 3×3×3 cm3; TE= 30, 50, 70, 120 ms; NA= 4 for each TE) data acquisition will be performed during repetitive single breath holds. Hepatocellular lipid (HCL) content will be calculated from ration of summed area of methylene and methyl resonance to that of water following the individual spin-spin relaxation correction as per cent of total tissue MRS signal (water + methylene + methyl).

Trial Locations

Locations (1)

Medical University Of Vienna, Department of Internal Medicine III; 🇦🇹 Vienna, Austria