Physiopathology of Sodium Retention in Acromegaly - Full Text View

Sponsor:	Assistance Publique - Hôpitaux de Paris
Collaborator:	Institut National de la Santé Et de la Recherche Médicale, France
Information provided by (Responsible Party):	Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:	NCT00531908

Purpose

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.

Condition	Intervention
Acromegaly	Drug: furosemide

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Physiopathology of Sodium Retention in Acromegaly

Resource links provided by NLM:

MedlinePlus related topics: High Blood Pressure

Drug Information available for: Furosemide

U.S. FDA Resources

Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome 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. ] [ Designated as safety issue: Yes ]

Secondary Outcome 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. ] [ Designated as safety issue: Yes ]
To study the difference of the intranasal potential [ Time Frame: before and after treatment of acromegaly. ] [ Designated as safety issue: Yes ]

Enrollment:	12
Study Start Date:	September 2007
Study Completion Date:	December 2009
Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: A To compare natriuretic effect of a single dose administration of amiloride (20 mg) in patients with acromegaly	Drug: furosemide furosemide Other Name: furosemide

Detailed Description:

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 BICETRE 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

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00531908

Locations

France
Hopital Bicetre
Paris, France, 75000

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

Institut National de la Santé Et de la Recherche Médicale, France

Investigators

Principal Investigator:

Peter KAMENICKY, MD

Assistance Publique - Hôpitaux de Paris

More Information

Publications:

Bihan H, Espinosa C, Valdes-Socin H, Salenave S, Young J, Levasseur S, Assayag P, Beckers A, Chanson P. Long-term outcome of patients with acromegaly and congestive heart failure. J Clin Endocrinol Metab. 2004 Nov;89(11):5308-13.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Kamenicky P, Blanchard A, Frank M, Salenave S, Letierce A, Azizi M, Lombès M, Chanson P. Body fluid expansion in acromegaly is related to enhanced epithelial sodium channel (ENaC) activity. J Clin Endocrinol Metab. 2011 Jul;96(7):2127-35. Epub 2011 Apr 20.

Responsible Party:	Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:	NCT00531908 History of Changes
Other Study ID Numbers:	P061012
Study First Received:	September 18, 2007
Last Updated:	December 6, 2011
Health Authority:	France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:

Growth Hormone
Epithelial sodium channel
Hypertension
A Furosemide
Nasal Mucosa

Additional relevant MeSH terms:

Acromegaly
Hypernatremia
Bone Diseases, Endocrine
Bone Diseases
Musculoskeletal Diseases
Hyperpituitarism
Pituitary Diseases
Hypothalamic Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Endocrine System Diseases

Water-Electrolyte Imbalance
Metabolic Diseases
Furosemide
Sodium Potassium Chloride Symporter Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on February 12, 2012