Cardiac Valve Complications in Prolactinomas Treated With Cabergoline (ValveCab)

April 14, 2008 updated by: Federico II University

Observational Study to Investigate the Prevalence of Cardiac Abnormalities and Valvular Regurgitation in Patients With Prolactinomas Treated Chronically With Cabergoline

Dopamine agonists are first-line agents for the treatment of prolactinomas (1) and Parkinson's disease (2). There is evidence supporting a causal relationship between the occurrence of drug-induced "restrictive" valvular heart disease and treatment with pergolide (3): in several cases, the valvulopathy improved when pergolide was discontinued (4). Valvular heart damage has also been reported with the ergot-derived dopamine agonists bromocriptine and cabergoline (5,6).

Two recent studies (7,8) have further demonstrated that both pergolide and cabergoline are associated with an increased risk of new cardiac valve regurgitation in patients treated for Parkinson's disease.

The valvular abnormalities seen with ergot-derived dopamine agonists are similar to those observed in patients receiving ergot alkaloid agents (such as ergotamine and methysergide) in the treatment of migraine, or fenfluramine and dexfenfluramine in the treatment of obesity. These abnormalities also closely resemble carcinoid-related valvulopathies (9).

Cardiac valve disease has never been reported in patients with prolactinomas who require treatment with dopamine-agonists even life-long (1). At variance with patients with Parkinson's disease, patients with prolactinomas are younger and are treated with an average dose of dopamine-agonists that is significantly lower (median bromocriptine dose 5 mg/day and median cabergoline dose 1 mg/week). Because of the young age of treatment beginning (most patients with microprolactinomas start dopamine-agonist treatment in early adulthood), treatment might be continued for over 3 decades: the cumulative risk of low doses of dopamine agonists for such a long period of treatment is currently unknown.

To assess the prevalence of cardiac valve disease in patients treated with cabergoline, we wish to perform an echocardiography screening in a large representative sample of patients with prolactinoma who were treated with cabergoline for at least 12 months and in a group of control subjects recruited prospectively. We wish to evaluate the severity of regurgitation for the mitral, aortic, and tricuspid valves. Changes in cardiac valve apparatus was compared with treatment duration and cumulative cabergoline dose.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Within one week from a clinical observation in the outpatient service, all patients will be admitted to the hospital for a complete endocrine screening, a cardiological visit that will include an electrocardiogram and an echocardiogram.

The endocrine profile will include measurement of IGF-I, PRL, FSH, LH, 17-β-estradiol, testosterone, FT3, FT4, TSH, and cortisol at 8.00 in the morning after an overnight fasting.

The clinical profile will include blood pressure measurement at the right arm, with the subjects in relaxed sitting position. The average of six measurements (three taken by each of two examiners, in the same day of echocardiography, between 8.00-9.00 in the morning) with a mercury sphygmomanometer will be used in all analysis. According with the seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (10), hypertension, if present, is classified as mild (Stage 1) when the SBP or DBP were between 140 and 159 mmHg and between 90 and 99 mmHg, respectively; severe (Stage 2) when the SBP or DBP were >160 and >100 mmHg respectively; pre-hypertension is defined as SBP >120¬ and <140 and DBP >80 and <90 mmHg. Heart rate will be also measured.

Study Type

Observational

Enrollment (Actual)

50

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • via S. Pansini 5 Naples, Italy, 80131
        • Department of Molecular and Clinical Endocrinology and Oncology, University Federico II of Naples

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

Three different study populations will be studied.

  • Group 1) Patients already receiving treatment with cabergoline for at least 12 months
  • Group 2) Newly diagnosed patients with hyperprolactinemia who never received treatment with dopamine-agonists
  • Group 3) Non hyperprolactinemic subjects matched with the patients for sex and age to be used as controls.

Description

Inclusion Criteria:

  • Patients with documented hyperprolactinemia receiving continuous treatment with cabergoline only for at least 12 months
  • Newly diagnosed patients with prolactinoma never previously receiving dopamine agonists treatment

Exclusion Criteria:

  • A history of cardiac valve abnormalities,
  • Previous use of anorectic drugs or other ergot-derived drugs,
  • Treatment with cabergoline for less than 12 months,
  • Valve calcification, valve regurgitation associated with annular dilatation or excessive leaflet motion,
  • Mitral regurgitation associated with left ventricular wall-motion abnormalities or left ventricular dilatation,
  • Withdrawal from cabergoline treatment for longer than 1 month, according with our treatment protocol (11).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
1
Patients already receiving treatment with cabergoline.
Drug: Cabergoline
According with our previous studies, in the patients with microprolactinoma and in those with non-tumoral hyperprolactinemia, cabergoline treatment was administered orally at a starting dose of 0.25 mg twice weekly for the first two weeks and then 0.5 mg twice weekly. After 2 months of treatment, dose adjustment was carried out every 2 months on the basis of serum PRL suppression.
Other Names:
  • Dostinex
2
healthy controls sex and age-matched with the patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Prevalence of regurgitation (graded as mild, moderate, severe) at any cardiac valve.
Time Frame: 9 months
9 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Federico II University

Investigators

  • Principal Investigator: Annamaria AL Colao, Prof., Federico II University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2007

Study Completion (Actual)

September 1, 2007

Study Registration Dates

First Submitted

April 13, 2007

First Submitted That Met QC Criteria

April 13, 2007

First Posted (Estimate)

April 16, 2007

Study Record Updates

Last Update Posted (Estimate)

April 16, 2008

Last Update Submitted That Met QC Criteria

April 14, 2008

Last Verified

October 1, 2007

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NeuroendoUnit-2

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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