Clinical trial NCT01375153: Brain Natriuretic Peptide Effects on Appetite Regulating Hormones and Endothelial Derived Peptides
Official title: Effects of Brain Natriuretic Peptide on Appetite-regulating Hormones and Endothelial-derived Peptides
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy
Keywords: BNP administration
appetite
ghrelin
PYY
Lead sponsor: Medical University of Vienna
Sponsor class: OTHER
First posted: 2011-06-17
Enrollment: 10
Sex: MALE
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: Chronic heart failure is accompanied by anorexia and increased release of B-type natriuretic peptide (BNP) from the ventricular myocytes. The pathophysiological mechanisms linking heart failure and appetite-regulation remain unknown. This study aims to examine the impact of exogenous BNP administration on subjective ratings of hunger and satiety, and on appetite-regulating hormones in a placebo-controlled cross-over study performed in ten healthy human volunteers.

Detailed description: This is a prospective, single blinded randomized, placebo-controlled, cross-over study, which will be conducted in ten healthy volunteers.

Each subject will participate in two study days/sessions, separated by a washout period of at least two weeks. The sessions will last approximately 4.5 hours. The subjects will come after having fasted overnight. Two intravenous cannulas will be placed in the right and left antecubital vein for infusions and blood sampling, respectively.

The subjects will receive intravenously once placebo and once 3.0 pmol/kg/min human active BNP (BNP-32) as a continuous intravenous infusion given during 4 hours (between time points 0 and 240 minutes). The order of study drugs will be randomized.

During the whole study session (lasting about 4.5 hours) the subject will remain fasted and confined to bed rest.

The changes in subjective ratings of hunger and satiety over time will be evaluated by 100 mm visual analog scales (VAS) half-hourly (between time points 0 and 240 minutes). Herewith the subjects rate their feeling of hunger (Hunger-VAS forms include the question: How hungry do you feel? Subjects are required to mark their feeling of hunger in a scale from 0 to 100 mm) and satiety (Satiety-VAS forms include the question: How satt do you feel? Subjects are required to mark their feeling of hunger in a scale from 0 to 100 mm).

Blood samples will be withdrawn twice at baseline (time points -5 minutes and 0 minutes) and hourly afterwards. Samples will be immediately cooled on ice, centrifuged at 3000 rpm for 10 minutes and then stored at -20°C for the later measurement of ghrelin, peptide YY, adiponectin, corticotropin, cortisol, adrenaline, noradrenaline, insulin, adrenomedullin, endothelin, copeptin, growth differentiation factor 15, BNP and atrial natriuretic peptide. All assays will be performed using commercial radioimmunoassays and enzyme-linked immunosorbent assays at the very end of the study with samples belonging to (both study days) one subject being measured within one kit.

The changes in VAS and hormone concentrations over time will be evaluated using repeated measurements analysis of variance (ANOVA) using the SPSS release 12.0.1 statistical software.

Eligibility criteria: Inclusion Criteria:

* Men aged 18 to 40 years
* written informed consent
* BMI \< 25 kg/m2
* no concomitant diseases
* BNP level within the normal range
* Normal renal function (serum creatinine of less then 1.2 mg/dL and/or creatinin clearance greater than 80ml/min)

Exclusion Criteria:

* systolic blood pressure \< 90 mmHg
* impaired glucose tolerance or diabetes mellitus
* hyperthyroidism, hypothyroidism
* hepatic, renal or cardiovascular diseases
* malignancies
* history of medical therapy within 3 weeks prior to enrolment into the study
* history of anaphylaxis

Primary outcomes:
measure: Changes in hunger scores on the visual analog scales (VAS) over time as compared to baseline (measured in mm)
timeFrame: Time points -5, 0, 30, 60, 90, 120, 150, 180, 210 and 240 minutes
measure: Changes in satiety scores on the VAS over time as compared to baseline (measured in mm)
timeFrame: Time points -5, 0, 30, 60, 90, 120, 150, 180, 210 and 240 minutes
measure: Changes in plasma concentrations of ghrelin and acylated ghrelin over time as compared to baseline
timeFrame: Timepoints -5, 0, 60, 120, 180 and 240 minutes.
measure: Changes in plasma concentrations of peptide YY (PYY) over time as compared to baseline
timeFrame: Timepoints -5, 0, 60, 120, 180 and 240 minutes.
Secondary outcomes:
measure: Changes in plasma concentrations of glucose and adiponectin over time as compared to baseline
timeFrame: During two study sessions lasting 4 hours each and performed at least two weeks apart. Blood samples will be taken twice at baseline and then hourly afterwards (between time-points 0 minutes and 240 minutes)
measure: Changes in plasma concentrations of cortisol, adrenaline and noradrenaline over time as compared to baseline
timeFrame: Timepoints -5, 0, 60, 120, 180 and 240 minutes.
measure: Changes in plasma concentrations of B-type natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) over time as compared to baseline
timeFrame: Timepoints -5, 0, 60, 120, 180 and 240 minutes.
measure: Changes in plasma concentrations of endothelial derived factors (endothelin, adrenomedullin and growth differentiation factor 15) over time as compared to baseline
timeFrame: Timepoints -5, 0, 60, 120, 180 and 240 minutes.
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Medical University of Vienna
city: Vienna
country: Austria
facility: AKH, Medical University of Vienna
Study officials:
affiliation: Medical University of Vienna
name: Anton Luger, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Vila G, Grimm G, Resl M, Heinisch B, Einwallner E, Esterbauer H, Dieplinger B, Mueller T, Luger A, Clodi M. B-type natriuretic peptide modulates ghrelin, hunger, and satiety in healthy men. Diabetes. 2012 Oct;61(10):2592-6. doi: 10.2337/db11-1466. Epub 2012 Jun 14.