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

NCT02115906 | Unknown DMC

• 1 other identifier: THIGHT_2
• Study Type: observational
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Acromegaly

Outcome Measures

Primary Outcomes (1)

• Changes in hepatic energy metabolism

  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.

  before & 3,6,9, and 12 months after initiation of therapy

Secondary Outcomes (1)

• Changes in hepatic lipid content

  before, as well as 3,6,9 &12 months after initiation of therapy

Other Outcomes (3)

• Changes in skeletal muscle energy metabolism

  before, as well as 3,6,9 and 12 months after initiation of therapy

• Changes in skeletal muscle lipid content

  before, as well as 3,6,9 and 12 months after initiation of therapy

• Changes in thyroid morphology

  before and 12 months after initiation of individual therapy

Study Arms (2)

Acromegalic patients

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

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

Healthy control subjects

Age and Body mass index matched control subjects will be investigated by 1H/31P magnetic resonance spectroscopy and oral glucose tolerance testing

Other: 1H/31P Magnetic Resonance Spectroscopy; Other: oral glucose tolerance testing

Interventions

1H/31P Magnetic Resonance Spectroscopy OTHER

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. Participants will be investigated lying in lateral position with the right lobe of the liver positioned over the coil.

Acromegalic patients; Healthy control subjects

oral glucose tolerance testing OTHER

In patients without overt diabetes, glucose tolerance will be assessed by an oral glucose tolerance test, routinely performed at the outpatients clinic. The test will be performed in the morning after an overnight fast of at least 8 hours. Blood will be drawn via a catheter placed in an antecubital vein of one arm. Blood samples for the assessment of glucose, insulin, C-peptide, free fatty acids and growth hormone will be drawn at baseline as well as 30, 60, 90 and 120 minutes after ingestion of 75g glucose in a solution. Concentrations of glucose, insulin and C-peptide will be used to derive parameters of insulin secretion and insulin sensitivity by mathematical modelling.

Acromegalic patients; Healthy control subjects

Thyroid sonography OTHER

In acromegalic patients thyroid morphology will be assessed at the outpatient clinic of the Division of Endocrinology and Metabolism, using standard ultrasound technique. Measurements will be performed by a well- experienced physician at baseline and at each follow up examination in an out-patient care setting.

Acromegalic patients

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

acromegalic patients and healthy controls matched for sex, age and body mass index

You may qualify if:

• age between 18-75 years

You may not qualify if:

• (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

Sponsors & Collaborators

• Medical University of Vienna: lead

Study Sites (1)

Medical University Of Vienna, Department of Internal Medicine III

Vienna, Vienna, 1090, Austria

RECRUITING

Related Publications (1)

• 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.

  PMID: 24647824 BACKGROUND

MeSH Terms

Conditions

Acromegaly

Condition Hierarchy (Ancestors)

Bone Diseases, Endocrine; Bone Diseases; Musculoskeletal Diseases; Hyperpituitarism; Pituitary Diseases; Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases

Study Officials

• Michael Krebs, MD, Prof.

  Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Peter Wolf, MD

CONTACT

00431404004311; peter.wolf@meduniwien.ac.at

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: ao. Univ. Prof. Dr. med. univ.

Study Record Dates

• First Submitted: April 11, 2014
• First Posted: April 16, 2014
• Study Start: August 1, 2014
• Primary Completion: May 1, 2017
• Study Completion: May 1, 2018
• Last Updated: September 27, 2016

Record last verified: 2016-09

Locations

AU (1)