Questa pagina è stata tradotta automaticamente e l'accuratezza della traduzione non è garantita. Si prega di fare riferimento al Versione inglese per un testo di partenza.

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

26 settembre 2016 aggiornato da: Prof. Dr. Michael Krebs, Medical University of Vienna

Assessment of Changes in Metabolic Activity in Liver & Skeletal Muscle in Patients Suffering From Acromegaly - a 31P/1H Magnetic Resonance Spectroscopy Pilot Study

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.

Panoramica dello studio

Stato

Sconosciuto

Condizioni

Intervento / Trattamento

Descrizione dettagliata

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.

Tipo di studio

Osservativo

Iscrizione (Anticipato)

24

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

  • Austria
      • Vienna, Austria, 1090
        • Reclutamento
        • Medical University of Vienna, Department of Internal Medicine III
        • Contatto:
        • Investigatore principale:
          • Michael Krebs, MD, Prof

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

Da 18 anni a 75 anni (Adulto, Adulto più anziano)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Metodo di campionamento

Campione non probabilistico

Popolazione di studio

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

Descrizione

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

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Modelli osservazionali: Caso di controllo
  • Prospettive temporali: Prospettiva

Coorti e interventi

Gruppo / Coorte
Intervento / Trattamento
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
Altro: 1H/31P Magnetic Resonance Spectroscopy
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.
Altro: oral glucose tolerance testing

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.

Altro: Thyroid sonography
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.
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
Altro: 1H/31P Magnetic Resonance Spectroscopy
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.
Altro: oral glucose tolerance testing

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.

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Changes in hepatic energy metabolism
Lasso di tempo: 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.
before & 3,6,9, and 12 months after initiation of therapy

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Changes in hepatic lipid content
Lasso di tempo: 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).
before, as well as 3,6,9 &12 months after initiation of therapy

Altre misure di risultato

Misura del risultato
Misura Descrizione
Lasso di tempo
Changes in skeletal muscle energy metabolism
Lasso di tempo: before, as well as 3,6,9 and 12 months after initiation of therapy
Resting-state ATP turnover will be measured using a ST experiment. The subjects will be lying in a supine position with the surface coil fixed underneath the right calf muscle. Baseline intramyocellular concentrations of phosphorous metabolites will be assessed based on T1 corrected partially relaxed baseline spectra (TR, 15 s; 16 averages). The exchange between γ-ATP and PCr (i.e., CK reaction), and between γ-ATP and Pi (i.e., ATP- synthesis) will be investigated.
before, as well as 3,6,9 and 12 months after initiation of therapy
Changes in skeletal muscle lipid content
Lasso di tempo: before, as well as 3,6,9 and 12 months after initiation of therapy
Intramyocellular lipid content will be assessed using localized single voxel 1H MRS as published by our studygroup[34]. STEAM sequence (VOI= 12x12x12 mm3; TE= 20 ms; TR= 4 sec, NA= 16) data acquisition will be performed in two volumes of interest positioned in soleus and tibialis anterior muscle. Separate spectra without water signal suppression (NA= 4) will be obtained from both muscle groups. Intramyocellular lipid content (IMCL) content will be calculated from ratio of area of methylene (1.25 ppm) to that of water following the individual spin-spin relaxation correction as per cent of tissue water MRS signal.
before, as well as 3,6,9 and 12 months after initiation of therapy
Changes in thyroid morphology
Lasso di tempo: before and 12 months after initiation of individual therapy
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.
before and 12 months after initiation of individual therapy

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Medical University of Vienna

Investigatori

  • Investigatore principale: Michael Krebs, MD, Prof., Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria

Pubblicazioni e link utili

La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.

Pubblicazioni generali

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio

1 agosto 2014

Completamento primario (Anticipato)

1 maggio 2017

Completamento dello studio (Anticipato)

1 maggio 2018

Date di iscrizione allo studio

Primo inviato

11 aprile 2014

Primo inviato che soddisfa i criteri di controllo qualità

15 aprile 2014

Primo Inserito (Stima)

16 aprile 2014

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Stima)

27 settembre 2016

Ultimo aggiornamento inviato che soddisfa i criteri QC

26 settembre 2016

Ultimo verificato

1 settembre 2016

Maggiori informazioni

Termini relativi a questo studio

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • THIGHT_2

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

Prove cliniche su 1H/31P Magnetic Resonance Spectroscopy

Cerca prove simili

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

CROs by country

CROs in Switzerland

Condizioni

Malattie rare

Interventi farmacologici

Supplementi dietetici

Sponsor / Collaboratori

Sedi

Sottoscrivi