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Acute Neuroendocrine Response to Intravenous Infusion of Diclofenac Sodium

Phase 4
Completed
Conditions
Hypopituitarism
Interventions
Drug: Intravenous Infusion of Diclofenac Sodium
Drug: Intravenous Infusion of Placebo
Registration Number
NCT05188131
Lead Sponsor
A.O.U. Città della Salute e della Scienza
Brief Summary

The effects of acute administration of non-steroidal anti-inflammatory drugs (NSAIDs) on the neuroendocrine regulation of hydro-electrolytic metabolism are not precisely known to date.

Although the mechanism by which NSAIDs favor the antidiuretic action of vasopressin (AVP) in the kidney has been partially elucidated, their influence on the mechanisms responsible for regulating its secretion are less known. The interactions between NSAIDs and natriuretic peptides are also not entirely certain.

The present pharmacological research study therefore aims to investigate, in a cohort of healthy subjects, the acute effects of intravenous infusion of diclofenac sodium on the neuroendocrine regulation systems of water and salt balance (i.e. the antidiuretic axis and the system of natriuretic peptides).

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
12
Inclusion Criteria
  • Any adult healthy subject (with age 20-50 years old) not meeting any of the exclusion criteria listed below
Exclusion Criteria
  • BMI < 18.5 kg/m2 or > 25 kg/m2
  • Any active pharmacological treatment
  • Pregnancy or breastfeeding
  • History of polyuria/polydipsia syndrome
  • History of dysionia
  • History of peptic disease
  • History of gastrointestinal bleeding
  • History of kidney disease
  • History of heart disease
  • History of asthma
  • Known allergy to NSAIDs
  • Any current acute medical condition

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Intravenous Infusion of Diclofenac SodiumIntravenous Infusion of Diclofenac SodiumIntravenous Infusion of Diclofenac Sodium in healthy subjects.
Intravenous Infusion of PlaceboIntravenous Infusion of PlaceboIntravenous Infusion of Placebo (isotonic saline) in healthy subjects.
Primary Outcome Measures
NameTimeMethod
Change in plasma copeptin levels between baseline and 45 minutes after diclofenac/placebo administrationFrom baseline (0 minutes) to 45 minutes after diclofenac/placebo administration

The response of the antidiuretic axis to the administration of intravenous diclofenac sodium, compared to placebo, is evaluated by measuring plasma copeptin (pmol/L) at baseline (0 minutes) and after 45 minutes from diclofenac/placebo administration.

Change in plasma copeptin levels between baseline and 120 minutes after diclofenac/placebo administrationFrom baseline (0 minutes) to 120 minutes after diclofenac/placebo administration

The response of the antidiuretic axis to the administration of intravenous diclofenac sodium, compared to placebo, is evaluated by measuring plasma copeptin (pmol/L) at baseline (0 minutes) and after 120 minutes from diclofenac/placebo administration.

Change in plasma MR-proANP levels between baseline and 30 minutes after diclofenac/placebo administrationFrom baseline (0 minutes) to 30 minutes after diclofenac/placebo administration

The response of the natriuretic peptide system to the administration of intravenous diclofenac sodium, compared to placebo, is evaluated by measuring plasma MR-proANP (pmol/L) at baseline (0 minutes) and after 30 minutes from diclofenac/placebo administration.

Change in plasma copeptin levels between baseline and 15 minutes after diclofenac/placebo administrationFrom baseline (0 minutes) to 15 minutes after diclofenac/placebo administration

The response of the antidiuretic axis to the administration of intravenous diclofenac sodium, compared to placebo, is evaluated by measuring plasma copeptin (pmol/L) at baseline (0 minutes) and after 15 minutes from diclofenac/placebo administration.

Change in plasma copeptin levels between baseline and 30 minutes after diclofenac/placebo administrationFrom baseline (0 minutes) to 30 minutes after diclofenac/placebo administration

The response of the antidiuretic axis to the administration of intravenous diclofenac sodium, compared to placebo, is evaluated by measuring plasma copeptin (pmol/L) at baseline (0 minutes) and after 30 minutes from diclofenac/placebo administration.

Change in plasma copeptin levels between baseline and 60 minutes after diclofenac/placebo administrationFrom baseline (0 minutes) to 60 minutes after diclofenac/placebo administration

The response of the antidiuretic axis to the administration of intravenous diclofenac sodium, compared to placebo, is evaluated by measuring plasma copeptin (pmol/L) at baseline (0 minutes) and after 60 minutes from diclofenac/placebo administration.

Change in plasma MR-proANP levels between baseline and 60 minutes after diclofenac/placebo administrationFrom baseline (0 minutes) to 60 minutes after diclofenac/placebo administration

The response of the natriuretic peptide system to the administration of intravenous diclofenac sodium, compared to placebo, is evaluated by measuring plasma MR-proANP (pmol/L) at baseline (0 minutes) and after 60 minutes from diclofenac/placebo administration.

Change in plasma copeptin levels between baseline and 90 minutes after diclofenac/placebo administrationFrom baseline (0 minutes) to 90 minutes after diclofenac/placebo administration

The response of the antidiuretic axis to the administration of intravenous diclofenac sodium, compared to placebo, is evaluated by measuring plasma copeptin (pmol/L) at baseline (0 minutes) and after 90 minutes from diclofenac/placebo administration.

Change in plasma copeptin levels between baseline and 240 minutes after diclofenac/placebo administrationFrom baseline (0 minutes) to 240 minutes after diclofenac/placebo administration

The response of the antidiuretic axis to the administration of intravenous diclofenac sodium, compared to placebo, is evaluated by measuring plasma copeptin (pmol/L) at baseline (0 minutes) and after 240 minutes from diclofenac/placebo administration.

Change in plasma MR-proANP levels between baseline and 15 minutes after diclofenac/placebo administrationFrom baseline (0 minutes) to 15 minutes after diclofenac/placebo administration

The response of the natriuretic peptide system to the administration of intravenous diclofenac sodium, compared to placebo, is evaluated by measuring plasma MR-proANP (pmol/L) at baseline (0 minutes) and after 15 minutes from diclofenac/placebo administration.

Change in plasma MR-proANP levels between baseline and 45 minutes after diclofenac/placebo administrationFrom baseline (0 minutes) to 45 minutes after diclofenac/placebo administration

The response of the natriuretic peptide system to the administration of intravenous diclofenac sodium, compared to placebo, is evaluated by measuring plasma MR-proANP (pmol/L) at baseline (0 minutes) and after 45 minutes from diclofenac/placebo administration.

Change in plasma MR-proANP levels between baseline and 120 minutes after diclofenac/placebo administrationFrom baseline (0 minutes) to 120 minutes after diclofenac/placebo administration

The response of the natriuretic peptide system to the administration of intravenous diclofenac sodium, compared to placebo, is evaluated by measuring plasma MR-proANP (pmol/L) at baseline (0 minutes) and after 120 minutes from diclofenac/placebo administration.

Change in plasma MR-proANP levels between baseline and 90 minutes after diclofenac/placebo administrationFrom baseline (0 minutes) to 90 minutes after diclofenac/placebo administration

The response of the natriuretic peptide system to the administration of intravenous diclofenac sodium, compared to placebo, is evaluated by measuring plasma MR-proANP (pmol/L) at baseline (0 minutes) and after 90 minutes from diclofenac/placebo administration.

Change in plasma MR-proANP levels between baseline and 240 minutes after diclofenac/placebo administrationFrom baseline (0 minutes) to 240 minutes after diclofenac/placebo administration

The response of the natriuretic peptide system to the administration of intravenous diclofenac sodium, compared to placebo, is evaluated by measuring plasma MR-proANP (pmol/L) at baseline (0 minutes) and after 240 minutes from diclofenac/placebo administration.

Secondary Outcome Measures
NameTimeMethod
Change in serum sodium levels between baseline and 120 minutes after diclofenac/placebo administrationFrom baseline (0 minutes) to 120 minutes after diclofenac/placebo administration

The response to the administration of intravenous diclofenac sodium, compared to placebo, in terms of glycometabolic and hydroelectrolyte biochemical balance was evaluated by measuring serum sodium (mmol/L) at baseline (0 minutes) and after 120 minutes from diclofenac/placebo administration.

Change in plasma MR-proADM levels between baseline and 15 minutes after diclofenac/placebo administrationFrom baseline (0 minutes) to 15 minutes after diclofenac/placebo administration

The response to the administration of intravenous diclofenac sodium, compared to placebo, in terms of glycometabolic and hydroelectrolyte biochemical balance was evaluated by measuring plasma MR-proADM (pmol/L) at baseline (0 minutes) and after 15 minutes from diclofenac/placebo administration.

Change in plasma MR-proADM levels between baseline and 120 minutes after diclofenac/placebo administrationFrom baseline (0 minutes) to 120 minutes after diclofenac/placebo administration

The response to the administration of intravenous diclofenac sodium, compared to placebo, in terms of glycometabolic and hydroelectrolyte biochemical balance was evaluated by measuring plasma MR-proADM (pmol/L) at baseline (0 minutes) and after 120 minutes from diclofenac/placebo administration.

Change in serum sodium levels between baseline and 45 minutes after diclofenac/placebo administrationFrom baseline (0 minutes) to 45 minutes after diclofenac/placebo administration

The response to the administration of intravenous diclofenac sodium, compared to placebo, in terms of glycometabolic and hydroelectrolyte biochemical balance was evaluated by measuring serum sodium (mmol/L) at baseline (0 minutes) and after 45 minutes from diclofenac/placebo administration.

Change in serum sodium levels between baseline and 60 minutes after diclofenac/placebo administrationFrom baseline (0 minutes) to 60 minutes after diclofenac/placebo administration

The response to the administration of intravenous diclofenac sodium, compared to placebo, in terms of glycometabolic and hydroelectrolyte biochemical balance was evaluated by measuring serum sodium (mmol/L) at baseline (0 minutes) and after 60 minutes from diclofenac/placebo administration.

Change in plasma MR-proADM levels between baseline and 45 minutes after diclofenac/placebo administrationFrom baseline (0 minutes) to 45 minutes after diclofenac/placebo administration

The response to the administration of intravenous diclofenac sodium, compared to placebo, in terms of glycometabolic and hydroelectrolyte biochemical balance was evaluated by measuring plasma MR-proADM (pmol/L) at baseline (0 minutes) and after 45 minutes from diclofenac/placebo administration.

Change in resistance at bioimpedance vector analysis between baseline and 240 minutes after diclofenac/placebo administrationFrom baseline (0 minutes) to 240 minutes after diclofenac/placebo administration

The response to the administration of intravenous diclofenac sodium, compared to placebo, in terms of bioimpedance vector analysis was evaluated by measuring resistance (Ohm) at baseline (0 minutes) and after 240 minutes from diclofenac/placebo administration.

Change in serum sodium levels between baseline and 15 minutes after diclofenac/placebo administrationFrom baseline (0 minutes) to 15 minutes after diclofenac/placebo administration

The response to the administration of intravenous diclofenac sodium, compared to placebo, in terms of glycometabolic and hydroelectrolyte biochemical balance was evaluated by measuring serum sodium (mmol/L) at baseline (0 minutes) and after 15 minutes from diclofenac/placebo administration.

Change in serum sodium levels between baseline and 30 minutes after diclofenac/placebo administrationFrom baseline (0 minutes) to 30 minutes after diclofenac/placebo administration

The response to the administration of intravenous diclofenac sodium, compared to placebo, in terms of glycometabolic and hydroelectrolyte biochemical balance was evaluated by measuring serum sodium (mmol/L) at baseline (0 minutes) and after 30 minutes from diclofenac/placebo administration.

Change in serum sodium levels between baseline and 90 minutes after diclofenac/placebo administrationFrom baseline (0 minutes) to 90 minutes after diclofenac/placebo administration

The response to the administration of intravenous diclofenac sodium, compared to placebo, in terms of glycometabolic and hydroelectrolyte biochemical balance was evaluated by measuring serum sodium (mmol/L) at baseline (0 minutes) and after 90 minutes from diclofenac/placebo administration.

Change in plasma MR-proADM levels between baseline and 30 minutes after diclofenac/placebo administrationFrom baseline (0 minutes) to 30 minutes after diclofenac/placebo administration

The response to the administration of intravenous diclofenac sodium, compared to placebo, in terms of glycometabolic and hydroelectrolyte biochemical balance was evaluated by measuring plasma MR-proADM (pmol/L) at baseline (0 minutes) and after 30 minutes from diclofenac/placebo administration.

Change in plasma MR-proADM levels between baseline and 90 minutes after diclofenac/placebo administrationFrom baseline (0 minutes) to 90 minutes after diclofenac/placebo administration

The response to the administration of intravenous diclofenac sodium, compared to placebo, in terms of glycometabolic and hydroelectrolyte biochemical balance was evaluated by measuring plasma MR-proADM (pmol/L) at baseline (0 minutes) and after 90 minutes from diclofenac/placebo administration.

Change in plasma MR-proADM levels between baseline and 60 minutes after diclofenac/placebo administrationFrom baseline (0 minutes) to 60 minutes after diclofenac/placebo administration

The response to the administration of intravenous diclofenac sodium, compared to placebo, in terms of glycometabolic and hydroelectrolyte biochemical balance was evaluated by measuring plasma MR-proADM (pmol/L) at baseline (0 minutes) and after 60 minutes from diclofenac/placebo administration.

Change in urine potassium levels between baseline and 240 minutes after diclofenac/placebo administrationFrom baseline (0 minutes) to 240 minutes after diclofenac/placebo administration

The response to the administration of intravenous diclofenac sodium, compared to placebo, in terms of glycometabolic and hydroelectrolyte biochemical balance was evaluated by measuring urine potassium (mmol/L) at baseline (0 minutes) and after 240 minutes from diclofenac/placebo administration.

Change in late-night salivary cortisol levels between 9 hours before and 15 hours after diclofenac/placebo administrationFrom 9 hours before to 15 hours after diclofenac/placebo administration

The influence the administration of intravenous diclofenac sodium, compared to placebo, on late-night salivary cortisol was evaluated by measuring late-night salivary cortisol (ng/ml) at 11 pm the day before diclofenac/placebo administration, and at 11 pm the day of diclofenac/placebo administration.

Change in serum sodium levels between baseline and 240 minutes after diclofenac/placebo administrationFrom baseline (0 minutes) to 240 minutes after diclofenac/placebo administration

The response to the administration of intravenous diclofenac sodium, compared to placebo, in terms of glycometabolic and hydroelectrolyte biochemical balance was evaluated by measuring serum sodium (mmol/L) at baseline (0 minutes) and after 240 minutes from diclofenac/placebo administration.

Change in plasma MR-proADM levels between baseline and 240 minutes after diclofenac/placebo administrationFrom baseline (0 minutes) to 240 minutes after diclofenac/placebo administration

The response to the administration of intravenous diclofenac sodium, compared to placebo, in terms of glycometabolic and hydroelectrolyte biochemical balance was evaluated by measuring plasma MR-proADM (pmol/L) at baseline (0 minutes) and after 240 minutes from diclofenac/placebo administration.

Change in urine sodium levels between baseline and 240 minutes after diclofenac/placebo administrationFrom baseline (0 minutes) to 240 minutes after diclofenac/placebo administration

The response to the administration of intravenous diclofenac sodium, compared to placebo, in terms of glycometabolic and hydroelectrolyte biochemical balance was evaluated by measuring urine sodium (mmol/L) at baseline (0 minutes) and after 240 minutes from diclofenac/placebo administration.

Change in phase angle at bioimpedance vector analysis between baseline and 240 minutes after diclofenac/placebo administrationFrom baseline (0 minutes) to 240 minutes after diclofenac/placebo administration

The response to the administration of intravenous diclofenac sodium, compared to placebo, in terms of bioimpedance vector analysis (BIVA) was evaluated by measuring phase angle (°) at baseline (0 minutes) and after 240 minutes from diclofenac/placebo administration.

Change in urine osmolality between baseline and 240 minutes after diclofenac/placebo administrationFrom baseline (0 minutes) to 240 minutes after diclofenac/placebo administration

The response to the administration of intravenous diclofenac sodium, compared to placebo, in terms of glycometabolic and hydroelectrolyte biochemical balance was evaluated by measuring urine osmolality (mOsm/kg) at baseline (0 minutes) and after 240 minutes from diclofenac/placebo administration.

Change in reactance at bioimpedance vector analysis between baseline and 240 minutes after diclofenac/placebo administrationFrom baseline (0 minutes) to 240 minutes after diclofenac/placebo administration

The response to the administration of intravenous diclofenac sodium, compared to placebo, in terms of bioimpedance vector analysis (BIVA) was evaluated by measuring reactance (Ohm) at baseline (0 minutes) and after 240 minutes from diclofenac/placebo administration.

Trial Locations

Locations (1)

AOU Città della Salute e della Scienza

🇮🇹

Torino, Piemonte, Italy

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