Clinical trial NCT00451672: The Therapeutic Effect of Bromocriptin in Patients With Primary Aldosteronism
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Hyperaldosteronism
Hypertension
Keywords: aldosteronism, bromocriptin, hypertension
Lead sponsor: National Taiwan University Hospital
Sponsor class: OTHER
First posted: 2007-03-23
Enrollment: 25
Sex: ALL
Minimum age (years): 20
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: we propose that bromocriptine may be an alternative treatment of primary aldosteronism, both APA and BAH.

Detailed description: Primary aldosteronism (PA), a common curable disease of hypertension, is characterized by inappropriate production of aldosterone, which is at least partially autonomous of the renin-angiotensin system. A recent clinical study reported that patients with PA experience a higher sate of a higher rate of cardiovascular events than those with essential hypertension(Corry and Tuck 2003; Milliez, Girerd et al. 2005). The prevalence of metabolic syndrome was higher in primary aldosteronism than in essential hypertension was also reported (Fallo, Veglio et al. 2006). The wide applying of the plasma aldosterone/plasma rennin activity (ARR) as a screening test among hypertensive patients have reported a much higher prevalence of this disease, up to 12% of hypertensive patients. In the past decade, an increase in diagnosis rate of PA has been observed in National Taiwan University Hospital, with an average of 15-20 newly diagnosis cases every year.

Idiopathic bilateral adrenal hyperplasia (BAH) and aldosterone-producing adenoma (APA) are the leading causes of primary aldosteronism. Unilateral adrenalectomy is the reasonable therapeutic option of APA and aldosterone antagonists usually brings about well blood pressure (BP) control in BAH. Not every APA patient would accept operation because of other medical conditions, or the cure rate of hypertension in APA after adrenalectomy is 50-70% in most studies. For patients with BAH, aldosterone antagonists are the first choice of treatment, however, intolerance to high dose of these medications is not uncommon. To our best knowledge, there is no alternative treatment for these patients.

Dopaminergic regulation of aldosterone secretion has been well demonstrated in normal subjects as well as patients with PA. We have shown that D2 receptor can down-regulate the transcription of aldosterone synthase (CYP11B2) via a specific PKC isoform and probably intracellular calcium level. Furthermore, there is a reciprocal change of the mRNA of D2 receptor and CYP11B2 in APA. D2 receptor has also been demonstrated in other neuroendocrine tumors, eg., pheochromocytoma, prolactinoma, GH-secreting adenoma ect. \[Camacho \& Mazzone 1999\] Administration of D2 agonist, bromocriptin (BMC), is a standard treatment of prolactinoma, either for pre-operative reduction of the tumors or for non-surgical patients \[Chattopadhyay et al., 2005\]. Reduction or shrinkage of prolactinoma has been observed in patients treated with BMC \[Biswas et al., 2005\]. Anti-proliferative effect and apoptosis of BMC have been demonstrated in several cell lines \[Wasko et al., 2004\]. Recently, we also demonstrated that BMC, in addition to decrease aldosterone secretion and expression of CYP11B2, could inhibit cell proliferation of H295 cells, an adrenocortical carcinoma cell line, with a down-regulation of ERK. In this context, we propose that BMC may be an alternative treatment of PA, both APA and BAH.

Eligibility criteria: Inclusion Criteria:

* 20-60y/o hyperaldosteronsim patients

Exclusion Criteria:

* Malignancy
* Bed-ridden
* Psychological disease

Primary outcomes:
measure: tumor size, blood pressure
Secondary outcomes:
measure: serum potassium, aldosterone, renine
Other outcomes:
Locations:
city: Taipei
country: Taiwan
facility: National Taiwan Univserty Hospital
Study officials:
affiliation: Internal Medicine, Natinal Taiwan University Hospital
name: Kwan-Dun Wu, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Internal Medicine, National Taiwan University Hospital
name: Vin-Cent Wu, MD
role: STUDY_DIRECTOR
References:
citation: Chang HW, Chu TS, Huang HY, Chueh SC, Wu VC, Chen YM, Hsieh BS, Wu KD. Down-regulation of D2 dopamine receptor and increased protein kinase Cmu phosphorylation in aldosterone-producing adenoma play roles in aldosterone overproduction. J Clin Endocrinol Metab. 2007 May;92(5):1863-70. doi: 10.1210/jc.2006-2338. Epub 2007 Feb 13.