Condition category
Nutritional, Metabolic, Endocrine
Date applied
11/07/2011
Date assigned
28/09/2011
Last edited
10/09/2015
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

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

Publication citations

Additional files

Editorial Notes