Cardiac and Skeletal Muscle Energy Metabolism in Abnormal Growth Hormone States

NCT00461240 | Completed

• 1 other identifier: 004604
• Study Type: observational
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

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

• 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.

Conditions

Acromegaly; Growth Hormone Deficiency

Keywords

heart; MRS; acromegaly; growth hormone

Study Arms (2)

acromegaly

growth hormone deficiency

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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

You may qualify if:

• 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
• 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
• Systolic blood pressure \< 180 mmHg, diastolic blood pressure \< 110 mmHg.

You may not qualify if:

• 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

Sponsors & Collaborators

• Barts & The London NHS Trust: lead

Study Sites (1)

St Bartholomew's Hospital

West Smithfield, London, EC1A 7BE, United Kingdom

Location

Biospecimen

Retention: SAMPLES WITH DNA

blood samples will be retained

MeSH Terms

Conditions

Acromegaly; Dwarfism, Pituitary

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; Dwarfism; Bone Diseases, Developmental; Hypopituitarism

Study Officials

• Marta Korbonits, MD PhD

  Barts and the London Medical School

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 16, 2007
• First Posted: April 17, 2007
• Study Start: June 1, 2007
• Study Completion: December 1, 2011
• Last Updated: July 26, 2012

Record last verified: 2012-07

Locations

GB (1)