Lymphatic dysfunction as a cause of calcium channel blocker oedema in post-menopausal women

INTERVENTION: Trade Name: Amlodipin Actavis Product Name: Amlodipin "Actavis" Pharmaceutical Form: Tablet INN or Proposed INN: AMLODIPINE MESILATE MONOHYDRATE CAS Number: 440358‐84‐9 Current Sponsor code: 300488 Other descriptive name: AMLODIPINE MESILATE MONOHYDRATE Concentration unit: mg milligram(s) Concentration type: range Concentration number: 5‐10 Pharmaceutical form of the placebo: Tablet Route of administration of the placebo: Oral use CONDITION: Calcium channel antagonist induced peripheral edema in post‐menopausal women. We hypothesize that this condition is partly due to impaired lymphatic function in these patients. ; MedDRA version: 18.0 Level: LLT Classification code 10067033 Term: Drug side effect System Organ Class: 100000004867 ; MedDRA version: 18.0 Level: LLT Classification code 10034570 Term: Peripheral edema System Organ Class: 100000004867 Therapeutic area: Body processes [G] ‐ Circulatory and Respiratory Physiological Phenomena [G09] PRIMARY OUTCOME: Main Objective: The aim with this study is to investigate the mechanism behind the oedema development often associated with treatment of cardiovascular disease with calcium channel blockers. The current belief is that a preferential arterial over venous dilation leads to increased fluid filtration. We will test this concept by measuring capillary filtration, which surprisingly has never been done before. The current belief will furthermore be challenged by also measuring the lymphatic removal of interstitial fluid during treatment with calcium channel blockers. Lymph vessels could potentially be an off‐target effect of the drugs and augment oedema formation. This might explain why some patients treated with these drugs develop oedemas.; Primary end point(s): Primary end‐points are: lymphatic contraction frequency, contraction wave velocity, lymphatic systolic pumping pressure, the time it takes for a vessel to refill after it has been emptied by manual massage and capillary fluid filtration rate. Secondary Objective: none Timepoint(s) of evaluation of this end point: Every single end point will first be evaluated after completion of the last subject trial. 28 weeks SECONDARY OUTCOME: Secondary end point(s): none Timepoint(s) of evaluation of this end point: none INCLUSION CRITERIA: Healthy post‐menopausal women, which means that it is 1 years since last menstruation and case of flushing. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 8 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 8