Plain English Summary
Background and study aims
Acromegaly is a relatively rare disorder, affecting 4-6 people per million per year. In the majority of cases, a swelling on the pituitary gland releases an excess of growth hormone (GH), which can cause the hands, feet, nose and jaw to enlarge and the skin to become greasy. The condition itself has often been present for some time before the diagnosis is made, and is frequently complicated by high blood pressure, diabetes, enlargement of the heart and sleep disturbance (typically manifesting as snoring). Left untreated, people with acromegaly have a higher risk of developing diseases such as angina, heart attacks and stroke, as well as suffering from problems directly related to the pituitary swelling (e.g. headaches and visual disturbance). Surgery by an experienced neurosurgeon remains the mainstay of treatment, although complete removal of the pituitary swelling is often not possible because of the risk of damage to important surrounding structures, including the nerves to the eyes. Accordingly, further treatment (either in the form of radiotherapy, drugs or, on occasion, both) is often required to control the condition. In recent years it has become standard clinical practice to consider medical treatment prior to surgery with a class of drug commonly referred to as somatostatin receptor ligands (SRLs). These drugs can lower GH levels and improve symptoms and in some instances this is associated with shrinkage of the pituitary swelling, which may improve the surgical outcome. Many centres now routinely offer ‘pre-treatment’ to newly diagnosed cases of acromegaly. However, it remains unclear as to how effective these drugs are in terms of correcting the sleep disturbance, high blood pressure, metabolic upset, blood vessel changes and heart enlargement of acromegaly. This study aims to examine the effectiveness of a drug called ‘Lanreotide Autogel’ in reversing blood pressure, cardiac and breathing pattern changes seen in many acromegaly patients before they proceed to surgery.
Who can participate?
Newly diagnosed patients with acromegaly, aged over 18, who have not undergone any previous medical or surgical treatment or radiotherapy for their acromegaly.
What does the study involve?
Participants are asked to score various symptoms of acromegaly (e.g. headache, sweating, fatigue, arthralgia, carpal tunnel syndrome) using a 5-point scale. A full physical examination is performed. Clinical assessments include height, weight, waist and hip circumference, blood pressure measurement, ring size and neck size. At the first visit, blood tests are carried out to confirm the diagnosis of acromegaly. Participants in whom the diagnosis is confirmed are then invited for a second visit during which a more detailed assessment is undertaken with hourly blood sampling to estimate average GH levels. Liver function, fasting glucose and lipid profiles are also checked. Detailed studies of the heart and blood vessels are performed using ultrasound and a magnetic resonance imaging (MRI) scan is performed to determine the pituitary tumour volume. Ultrasound scans of the liver and gallbladder are performed to look for evidence of gall stones and gallbladder polyps. The former can sometimes develop in patients receiving treatment with SRLs and so it is helpful for us to know if these are already present before treatment begins. Participants also undergo overnight sleep studies (polysomnography) to determine the severity of their sleep disturbance. All participants will receive an injection of short-acting SRL octreotide to gauge their likely response to a longer course of SRL treatment. Participants are then treated with the longer acting Lanreotide Autogel, with the dose determined based on their response to octreotide. At each visit, patients are asked to re-score their acromegaly symptoms. At the end of the study, participants are assessed again, as outlined above.
What are the possible benefits and risks of participating?
Not provided at time of registration.
Where is the study run from?
University of Cambridge (UK).
When is study starting and how long is it expected to run for?
March 2004 to March 2014.
Who is funding the study?
IPSEN Fund, National Institute for Health Research, and Cambridge Biomedical Research Centre.
Who is the main contact?
Dr Mark Gurnell
mg299@medschl.cam.ac.uk
Trial website
Contact information
Type
Scientific
Primary contact
Dr Mark Gurnell
ORCID ID
Contact details
Institute of Metabolic Science and Department of Medicine
University of Cambridge
Box 289
Addenbrooke's Hospital
Hills Road
Cambridge
CB2 0QQ
United Kingdom
+44 (0)1223 245 151
mg299@medschl.cam.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
v.3 December 2009
Study information
Scientific title
A comprehensive study of clinical, biochemical, radiological, cardiovascular and sleep parameters in an unselected cohort of patients with newly diagnosed ACROmegaly undergoing Pre-surgical somatostatin Analogue Therapy with Lanreotide Autogel® (ACROPAT)
Acronym
ACROPAT
Study hypothesis
Medical therapy with Lanreotide Autogel® may improve biochemical parameters like growth hormone (GH) and Insulin-like growth factor 1 (IGF-1) levels which may benefit a comprehensive improvement in radiological, sleep and cardiovascular sequelae of acromegaly in a newly diagnosed acromegaly cohort
Ethics approval
Cambridgeshire 2 Research Ethics Committee, 09/12/2003, ref: 03/354
Study design
Prospective open-label cohort study
Primary study design
Interventional
Secondary study design
Non randomised study
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Acromegaly and medical pre treatment with Lanreotide Autogel®
Intervention
Phase 1: Baseline assessments
1. Clinical
Subjects will be asked to score various symptoms of acromegaly (e.g. headache, sweating, fatigue, arthralgia, carpal tunnel syndrome) using a 5-point scale (ranging from 0 = not present to 4 = severe/incapacitating). A full physical examination will be performed. Clinical assessments include height, weight, waist and hip circumference, blood pressure measurement, ring size and neck size estimations.
2. Biochemical
At the first visit, the diagnosis of acromegaly will be confirmed with blood tests, including a glucose challenge test. Those subjects in whom the diagnosis is confirmed will then be invited for a second visit during which a more detailed characterisation of residual pituitary status will be undertaken together with a growth hormone (GH) day profile (1 hourly blood sampling from 09:00 hrs - 17:00 hrs) to permit an estimate of average GH levels pre-treatment. Liver function, fasting glucose and lipid profiles will also be checked.
3. Cardiovascular
Detailed studies of the heart and blood vessels using ultrasound will be performed in conjunction with the Clinical Pharmacology Unit at Addenbrooke's Hospital.
4. Radiological
During the second visit, magnetic resonance imaging (MRI) of the pituitary fossa will be performed to permit accurate determination of pituitary tumour volume.
Ultrasound of the liver and gallbladder will also be performed to look for evidence of gall stones and gallbladder polyps. The former can sometimes develop in patients receiving treatment with SRLs and so it is helpful for us to know if these are already present before treatment is commenced.
5. Sleep disturbance
All subjects will be invited to the internationally recognised Respiratory Support and Sleep Centre (RSSC), Papworth Hospital for evidence of sleep disturbance. Patients will undergo formal overnight sleep studies (so-called polysomnography) to determine the degree/severity of sleep-disordered breathing.
Phase 2: Somatostatin analogue administration and interim assessments
At completion of the baseline assessments, all subjects will be started on an injection of subcutaneous (sc) octreotide 100mcg to gauge their likely response to a longer course of SRL therapy - octreotide is a short-acting SRL. Following a repeat GH series and IGF-1 measurement patients will be commenced on the longer acting depot preparation Lanreotide Autogel®, with the dose (60, 90 or 120mg by deep subcutaneous injection every 4 weeks) determined on the basis of mean GH level and observed response to the octreotide test dose.
Repeat GH series and IGF-1 measurements will be performed at 12 weeks to determine whether further dose adjustments are necessary.
At each visit, patients will be asked to re-score their symptoms of acromegaly.
Phase 3: Post-treatment assessments
At the completion of the study (6 months post-transition to Lanreotide Autogel®), subjects will be invited to attend for clinical, biochemical, cardiovascular, radiological and sleep-apnoea status re-assessment, as outlined above
Intervention type
Drug
Phase
Not Applicable
Drug names
Lanreotide Autogel®
Primary outcome measures
To determine the extent to which pre-surgical medical treatment with the SRL Lanreotide Autogel® ameliorates/reverses the following in newly diagnosed previously untreated acromegaly subjects:
1. Sleep disordered breathing
2. Cardiac hypertrophy and dysfunction
3. Hypertension and arterial dysfunction
Secondary outcome measures
To determine the extent to which pre-surgical medical treatment with the SRL Lanreotide Autogel®:
1. Reduces GH and IGF1 levels
2. Reduces pituitary tumour volume
3. Corrects 'metabolic dysfunction'
4. Induces biliary 'sludge'/gallstone formation
Overall trial start date
01/03/2004
Overall trial end date
01/03/2014
Reason abandoned
Eligibility
Participant inclusion criteria
1. Treatment naive newly diagnosed subjects with biochemically confirmed acromegaly
2. Males and females
3. More than 18 years of age
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
40
Participant exclusion criteria
Subjects who had prior medical therapy, surgery or radiotherapy or sight-threatening tumours requiring urgent surgical decompression
Recruitment start date
01/03/2004
Recruitment end date
01/03/2014
Locations
Countries of recruitment
United Kingdom
Trial participating centre
University of Cambridge
Cambridge
CB2 0QQ
United Kingdom
Sponsor information
Organisation
Addenbrooke's NHS Trust R&D
Sponsor details
Cambridge University Hospitals NHS Foundation Trust
Box 277
Hills Road
Cambridge
CB2 0QQ
Cambridge
CB2 0QQ
United Kingdom
-
sylvie.robinson@addenbrookes.nhs.uk
Sponsor type
Not defined
Website
Funders
Funder type
Industry
Funder name
IPSEN Fund (UK)
Alternative name(s)
Funding Body Type
private sector organisation
Funding Body Subtype
other non-profit
Location
United Kingdom
Funder name
National Institute for Health Research (UK)
Alternative name(s)
NIHR
Funding Body Type
government organisation
Funding Body Subtype
Federal/National Government
Location
United Kingdom
Funder name
Cambridge Biomedical Research Centre (UK)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary