Official Title: “Physiopathology of Sodium Retention in Acromegaly”

Acromegaly is a disease due to an excess of growth hormone that abnormally occurs in adulthood. It is due to a benign (non cancerous) tumor located in a particular part of the brain that secretes several hormones, the hypophysis. The excess of growth hormones in adults induces an increase in bone (resulting in large enlargement of extremities), and organs. The disease is complicated by the apparition of cardiovascular events including retention of water, salt in the tissues and increase in blood pressure, that altogether might major the mortality of the patients. The investigators recently got experimental data suggesting that the retention of water and salt is mainly due to the activation by the growth hormone of a renal transporter of sodium. Because this transporter is highly sensitive to amiloride, a well know diuretic, the investigators hypothesize that this drug will be very efficient in treating the hypertension in patients, as compared to another diuretic, furosemide.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Uncontrolled, Single Group Assignment, Efficacy Study

Study Primary Completion Date: September 2009

To prove this, we compared the response to amiloride administrated before and after treatment of acromegaly in the same subject. We will also compare the response to furosemide administrated before and after treatment of acromegaly in the same subject. We expected that the response to amiloride will be greater before than after treatment, while the response to furosemide will be lesser before than after treatment.

Detailed Description:

Definition: Extended description of the protocol, including information not already contained in other fields, such as comparison(s) studied. Patients will be recruited in the Department of Endocrinology and Reproductive diseases in Bicêtre University Hospital and will be explored in the Centre for Clinical Investigation of HEGP. Investigations will be performed during 4 separate day-hospital stays (2 pre-treatment and 2 post treatment) in the CIC of HEGP. The tests will consist of blood and urine sample collections before and after a single dose administration of furosemide or amiloride. The tests will be performed before treatment of acromegaly in random order and separated by 48hours, interval performed before treatment, and repeated in the same order after normalization of IGF1 by appropriate treatment.

The study will last for 2 years, with a 12 months maximal participation of each patient

Intervention(s) in this Clinical Trial

• Drug: furosemide
  • furosemide

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: A
  • To compare natriuretic effect of a single dose administration of amiloride (20 mg) in patients with acromegaly

Primary Measures

• To compare natriuretic effect of a single dose administration of amiloride (20 mg) in patients with acromegaly
  • Time Frame: before and after treatment of acromegaly.
    Safety Issue?: Yes

Secondary Measures

• To compare natriuretic effect of a single dose of furosemide (bolus 5 mg, then 10 mg over 2 hrs) in patients with acromegaly
  • Time Frame: before and after treatment of acromegaly.
    Safety Issue?: Yes
• To study the difference of the intranasal potential
  • Time Frame: before and after treatment of acromegaly.
    Safety Issue?: Yes

Inclusion Criteria:

• age 18 to 75 yrs
• proven evolutive acromegalia with indication of treatment (surgical or medical)
• controlled blood pressure (systolic BP < 140 mmHg et diastolic BP < 90 mmHg)
• signed informed consent
• efficient contraception in women

Exclusion Criteria:

• edematous state unrelated to acromegaly
• history of sulfamide intolerance
• hemoglobin < 8g/dL
• pregnant or breastfeeding women
• inability to give informed consent
• blood donation in the preceding 3 months

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 75 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Overall Clinical Trial Officials and Contacts

Peter KAMENICKY, MD Principal Investigator Assistance Publique - Hôpitaux de Paris  

Overall Contact: Peter KAMENICKY, MD +33 (0)1 45 21 37 05 

Information obtained from ClinicalTrials.gov on August 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00531908

Study ID Number: P061012

ClinicalTrials.gov Identifier: NCT00531908

Health Authority: France: Ministry of Health

Research department connected to the clinical department of endocrinology