Prolactinomas Clinical Trial
Official title:
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.
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.
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Observational Model: Case Control, Time Perspective: Prospective
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Recruiting |
NCT01620138 -
Expression Profile of Somatostatin Receptors and Dopamine Receptor 2 in Non-functioning Pituitary Adenomas and Resistant Prolactinomas: Correlation With in Vivo Response to Pasireotide and Cabergoline
|
Phase 2/Phase 3 | |
| Completed |
NCT00939523 -
Targeted Therapy With Lapatinib in Patients With Recurrent Pituitary Tumors Resistant to Standard Therapy
|
Phase 2 |