AcromegalyNCT02115906
Assessment of Changes in Metabolic Activity in Liver & Skeletal Muscle in Patients Suffering From Acromegaly
An observational study of Acromegaly, run by Medical University of Vienna at 1 site in Austria.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Acromegaly
- What is being tested?
- 1H/31P Magnetic Resonance Spectroscopy, oral glucose tolerance testing and Thyroid sonography
- Type of treatment
- Pill or oral medicine
- How many people
- 24 participants
- Where
- 1 siteAustria
- Study dates
- Aug 2014to May 2018
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: acromegalic patients and healthy controls matched for sex, age and body mass index
Who may be able to join
- age between 18-75 years
Who cannot join
- (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
Show all 11Show fewer
- severe liver disorders (plasma transaminases elevated > 3fold)
- any acute inflammatory disease within 2 weeks prior the study
- pregnancy
- nursing
- clinically relevant anemia
Trial locations and contacts
1 site in 1 country.
Austria1 site, 1 recruiting
- Recruiting
Medical University Of Vienna, Department of Internal Medicine III
Vienna, State of Vienna, 1090
Peter Wolf, MD, 00431404004311, peter.wolf@meduniwien.ac.at
Michael Krebs, MD, Prof
About this study
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
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.
Read the 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.
- Conditions
- Acromegaly
- Being tested
- 1H/31P Magnetic Resonance Spectroscopy, oral glucose tolerance testing, Thyroid sonography
- Medical subject headings
- Acromegaly
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
1H/31P Magnetic Resonance SpectroscopyOther
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.
oral glucose tolerance testingOther
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.
Thyroid sonographyOther
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Other: 1H/31P Magnetic Resonance Spectroscopy; Other: oral glucose tolerance testing |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: before & 3,6,9, and 12 months after initiation of therapy
Secondary outcomes (1)
Changes in hepatic lipid content
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).
Measured: before, as well as 3,6,9 &12 months after initiation of therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Apr 2014 (estimated)
- Study startAug 2014
- Primary completionMay 2017 (estimated)
- Study completionMay 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AcromegalyStudies of the same condition, open and under way.
- More trials run by Medical University of ViennaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Medical University of Vienna
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Prof. Dr. Michael Krebs, Medical University of Vienna
- Investigators
- Michael Krebs, MD, Prof., Principal investigator, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02115906
- Sponsor's protocol ID
- THIGHT_2
- Status last verified
- Sep 2016
- First submitted
- 11 Apr 2014
- Last updated
- 27 Sep 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 24647824
Study at a glance
From the registry record, last updated by the sponsor on 27 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02115906
- Acronym / sponsor ID
- THIGHT_2
- Conditions
- Acromegaly
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Medical University of ViennaUniversity, hospital or other
- Study start
- Aug 2014
- Primary completion
- May 2017 (estimated)
- Study completion
- May 2018 (estimated)
- First posted
- 16 Apr 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Acromegalic patients | – | Other: 1H/31P Magnetic Resonance Spectroscopy, Other: oral glucose tolerance testing, Other: Thyroid sonographyAcromegalic 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 | – | Other: 1H/31P Magnetic Resonance Spectroscopy, Other: oral glucose tolerance testingAge and Body mass index matched control subjects will be investigated by 1H/31P magnetic resonance spectroscopy and oral glucose tolerance testing |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- acromegalic patients and healthy controls matched for sex, age and body mass index
Key inclusion criteria (1 listed)
- age between 18-75 years
Key exclusion criteria (11 listed)
- (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].
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 1H/31P Magnetic Resonance SpectroscopyThe 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. | Other | Acromegalic patients, Healthy control subjects |
| oral glucose tolerance testingIn 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. | Other | Acromegalic patients, Healthy control subjects |
| Thyroid sonographyIn 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. | Other | Acromegalic patients |
Primary outcome
Changes in hepatic energy metabolism
Time frame: 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.
1 secondary outcome
Changes in hepatic lipid content
Time frame: before, as well as 3,6,9 &12 months after initiation of therapy
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Sep 2016.
- Background: PubMed 24647824Valkovic 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Krebs, MD, Prof. principal investigator
Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Acromegaly, run by Medical University of Vienna at 1 site in Austria.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 27 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Austria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Peter Wolf, MD (00431404004311, peter.wolf@meduniwien.ac.at), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in hepatic energy metabolism (time frame: before & 3,6,9, and 12 months after initiation of therapy). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02115906, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Sep 2016.