Clinical trial NCT02115906: Assessment of Changes in Metabolic Activity in Liver & Skeletal Muscle in Patients Suffering From Acromegaly
Official title: Assessment of Changes in Metabolic Activity in Liver & Skeletal Muscle in Patients Suffering From Acromegaly - a 31P/1H Magnetic Resonance Spectroscopy Pilot Study
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Acromegaly
Lead sponsor: Medical University of Vienna
Sponsor class: OTHER
First posted: 2014-04-16
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: acromegalic patients and healthy controls matched for sex, age and body mass index

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.

Eligibility criteria: Inclusion Criteria:

* age between 18-75 years

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

Primary outcomes:
measure: Changes in hepatic energy metabolism
timeFrame: before & 3,6,9, and 12 months after initiation of therapy
Secondary outcomes:
measure: Changes in hepatic lipid content
timeFrame: before, as well as 3,6,9 &12 months after initiation of therapy
Other outcomes:
measure: Changes in skeletal muscle energy metabolism
timeFrame: before, as well as 3,6,9 and 12 months after initiation of therapy
measure: Changes in skeletal muscle lipid content
timeFrame: before, as well as 3,6,9 and 12 months after initiation of therapy
measure: Changes in thyroid morphology
timeFrame: before and 12 months after initiation of individual therapy
Locations:
city: Vienna
country: Austria
facility: Medical University Of Vienna, Department of Internal Medicine III
Study officials:
affiliation: Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria
name: Michael Krebs, MD, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Valkovic L, Gajdosik M, Traussnigg S, Wolf P, Chmelik M, Kienbacher C, Bogner W, Krebs M, Trauner M, Trattnig S, Krssak M. Application of localized (3)(1)P MRS saturation transfer at 7 T for measurement of ATP metabolism in the liver: reproducibility and initial clinical application in patients with non-alcoholic fatty liver disease. Eur Radiol. 2014 Jul;24(7):1602-9. doi: 10.1007/s00330-014-3141-x. Epub 2014 Mar 20.