Cardiac and Skeletal Muscle Energy Metabolism in Abnormal Growth Hormone States

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Marta Korbonits, Barts & The London NHS Trust
ClinicalTrials.gov Identifier:
NCT00461240
First received: April 16, 2007
Last updated: July 24, 2012
Last verified: July 2012
  Purpose

Growth hormone (GH) is important for growth in childhood, but also has important effects on a number of tissues throughout life. GH deficiency and GH excess (acromegaly, caused by a pituitary tumour) are both cause serious abnormalities of metabolism and long−standing abnormal GH status causes abnormal heart function. In both cases cardiovascular disease is a leading cause of early (premature) death. In the current study we wish to investigate the energy status of the heart in patients with GH excess and deficiency and compare that with age−matched controls. We will perform a blood test to study metabolic parameters. We will perform measurements before treatment, after normalisation of improvement of GH levels and 2 years after start of treatment.

Objectives

  1. Determine cardiac and skeletal muscle energy metabolism in patients with GH excess (=acromegaly) or GH deficiency and detect changes after normalisation of GH and IGF−1 levels. (IGF−I is a hormone directly influenced by GH)
  2. To correlate muscle energy metabolism parameters to GH and IGF−1 status in the control subjects and in both patient groups
  3. Determine the prevalence of coronary artery calcifications in patients with GH excess and GH deficiency and correlate this with their metabolic status
  4. To correlate coronary artery calcifications to abdominal obesity. Patients will be identified by Endocrinology physicians involved in the study in outpatients clinics or Endocrine wards and they will receive standard care for their disease. Tests related to endocrine hormone abnormalities will be performed as usual clinical practice. The study will involve three 3−hour visits to the Oxford Research Centre and two 1−hour visits to London Scanning Centre.

The visits at the Oxford research centre will include Cardiac and skeletal investigations

  • Standard cardiac MRI will be used to measure right and left ventricular morphology and global function.
  • 31P Magnetic Resonance Spectroscopy (MRS) to monitor heart muscle energy levels (by measuring intracellular PCr and ATP in heart muscle).
  • Heart failure severity (so called 'NYHA status') will be determined from the 6 min walk test.
  • Peak oxygen uptake will be estimated from a metabolic gas exchange analysis performed during maximal treadmill exercise testing.
  • Skeletal muscle MR imaging and spectroscopy will be performed at rest and during exercise.
  • Fasting blood test will be performed, see details in protocol.
  • Electrocardiogram (ECG)
  • Epworth Sleepiness Scale questionnaire and 5 point test for sleep apnoea The visits at the London Scanning Centre will include
  • Electron beam coronary CT (EBCT) to assess coronary disease. The number of coronary disease lesions will be measured in several coronary arteries and values will add up to an overall score. In addition a single picture will be taken at the level of the umbilicus (belly button) to measure fat tissue within the abdomen. Patient selection: Patients will be recruited at St. Bartholomew's Hospital (Dr P. Jenkins and Prof. A. Grossman), King's Hospital (Dr S. Aylwin) and St Thomas's Hospital (Dr P. Carroll) in London, Royal Free Hospital (Prof P. Boloux), the John Radcliffe Hospital Oxford (Prof J. Wass), Addenbrooks Hospital Cambridge (Dr H. Simpson), Sheffield (Dr J. Newell−Price), and Stroke−on−Trent (Prof R. Clayton) from the Endocrine Wards and outpatient clinics. This constitutes a large recruitment base. We estimate that 45 new acromegaly patients and 60−80 new GHD patients per year will be screened. Patients will be selected on the basis of clinical diagnosis of acromegaly or GH deficiency (see details of these in the formal protocol).

Patients will be managed according to the clinical protocols of the referring centre.

The patients will have a report of their investigation results with their treating physicians.

Control subjects will be selected from the general population via advertisements. They will undergo all tests in the Oxford centre once.

Expected value of results:

These studies will increase our knowledge of the metabolic changes associated with GH excess and GH deficiency, which can lead to increased cardiac morbidity and mortality in both cases. Our studies will help to clarify the mechanism of abnormal cardiac function. The study has been powered to have appropriate number of subjects within a two year period, therefore we anticipate that it will last from start to finish 4 years.


Condition
Acromegaly
Growth Hormone Deficiency

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Cardiac and Skeletal Muscle Energy Metabolism in Abnormal Growth Hormone States

Resource links provided by NLM:


Further study details as provided by Barts & The London NHS Trust:

Biospecimen Retention:   Samples With DNA

blood samples will be retained


Enrollment: 25
Study Start Date: June 2007
Study Completion Date: December 2011
Groups/Cohorts
acromegaly
growth hormone deficiency

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Patients with growth hormone excess (acromegaly) or growth hormone deficiency

Criteria

Inclusion Criteria:

for acromegaly

  • Clinical and biochemical diagnosis of acromegaly. Thyroid and glucocorticoid replacement if necessary stable for at least 4 weeks before the study. Gonadotrophin status will be recorded and whenever possible patients will be studied in the same status
  • Males and females aged 18-70 years willing to give informed consent
  • At least 6 months after the onset of symptoms of acromegaly and on stable medication for heart failure treatment (if any) for at least 4 weeks prior to inclusion into the study
  • Systolic blood pressure < 180 mmHg, diastolic blood pressure < 110 mmHg.

for GHD

  • Clinical and biochemical diagnosis of GHD. All hormones replaced (if clinically necessary) except GH. Thyroid and glucocorticoid replacement if necessary stable for at least 4 weeks before the study. Gonadotrophin status will be recorded and whenever possible patients will be studied in the same status
  • Males and females aged 18-70 years willing to give informed consent
  • At least 6 months after the onset of symptoms of acromegaly and on stable medication for heart failure treatment (if any) for at least 4 weeks prior to inclusion into the study
  • Systolic blood pressure < 180 mmHg, diastolic blood pressure < 110 mmHg.

Exclusion Criteria:

for acromegaly

  • Change in medication in the preceding 4 weeks
  • Patients on subcutaneous insulin therapy
  • Hyperthyroidism
  • Not being in sinus rhythm
  • Unstable angina pectoris and decompensated heart failure (define as NYHA 3-4)
  • Clinically significant valvular disease, clinically significant chronic obstructive pulmonary disease
  • History of myocardial infarction or stroke within the last 6 months, major cardiac surgery within the last 6 months
  • Significant history of drug- or alcohol abuse or unable to give informed consent
  • Any other significant surgical or medical condition which would considerably affect results in view of the identifying clinician
  • Typical contraindication for MR (e.g. metal implants in delicate positions, aneurysm clips, shrapnel injuries, pacemakers, internal defibrillators and severe claustrophobia)
  • Pregnancy

for GHD

  • Change in medication in the preceding 4 weeks
  • Previous history of acromegaly
  • Child-hood onset GHD
  • Patients on subcutaneous insulin therapy metformin probably an exclusion
  • Hyperthyroidism
  • Not being in sinus rhythm
  • Unstable angina pectoris and decompensated heart failure (define as NYHA 3-4)
  • Clinically significant valvular disease, clinically significant chronic obstructive pulmonary disease
  • History of myocardial infarction or stroke within the last 6 months, major cardiac surgery within the last 6 months?
  • Significant history of drug- or alcohol abuse or unable to give informed consent
  • Any other significant surgical or medical condition which would considerably affect results in view of the identifying clinician
  • Typical contraindication for MR (e.g. metal implants in delicate positions, aneurysm clips, shrapnel injuries, pacemakers, internal defibrillators and severe claustrophobia)
  • Pregnancy
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00461240

Locations
United Kingdom
St Bartholomew's Hospital
West Smithfield, London, United Kingdom, EC1A 7BE
Sponsors and Collaborators
Barts & The London NHS Trust
Investigators
Principal Investigator: Marta Korbonits, MD PhD Barts and the London Medical School
  More Information

No publications provided

Responsible Party: Marta Korbonits, Professor, Barts & The London NHS Trust
ClinicalTrials.gov Identifier: NCT00461240     History of Changes
Other Study ID Numbers: 004604
Study First Received: April 16, 2007
Last Updated: July 24, 2012
Health Authority: United Kingdom: Research Ethics Committee

Keywords provided by Barts & The London NHS Trust:
heart
MRS
acromegaly
growth hormone

Additional relevant MeSH terms:
Dwarfism, Pituitary
Acromegaly
Dwarfism
Bone Diseases, Developmental
Bone Diseases
Musculoskeletal Diseases
Bone Diseases, Endocrine
Hypopituitarism
Pituitary Diseases
Hypothalamic Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Endocrine System Diseases
Hyperpituitarism
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 16, 2014