Acute Neuroendocrine Response to Intravenous Infusion of Diclofenac Sodium

NCT05188131 | Completed Phase 4 DMC

• 1 other identifier: NR-DICLO
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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).

Conditions

Hypopituitarism

Outcome Measures

Primary Outcomes (14)

• Change in plasma copeptin levels between baseline and 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.

  From baseline (0 minutes) to 15 minutes after diclofenac/placebo administration

• Change in plasma copeptin levels between baseline and 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.

  From baseline (0 minutes) to 30 minutes after diclofenac/placebo administration

• Change in plasma copeptin levels between baseline and 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.

  From baseline (0 minutes) to 45 minutes after diclofenac/placebo administration

• Change in plasma copeptin levels between baseline and 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.

  From baseline (0 minutes) to 60 minutes after diclofenac/placebo administration

• Change in plasma copeptin levels between baseline and 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.

  From baseline (0 minutes) to 90 minutes after diclofenac/placebo administration

• Change in plasma copeptin levels between baseline and 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.

  From baseline (0 minutes) to 120 minutes after diclofenac/placebo administration

• Change in plasma copeptin levels between baseline and 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.

  From baseline (0 minutes) to 240 minutes after diclofenac/placebo administration

• Change in plasma MR-proANP levels between baseline and 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.

  From baseline (0 minutes) to 15 minutes after diclofenac/placebo administration

• Change in plasma MR-proANP levels between baseline and 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.

  From baseline (0 minutes) to 30 minutes after diclofenac/placebo administration

• Change in plasma MR-proANP levels between baseline and 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.

  From baseline (0 minutes) to 45 minutes after diclofenac/placebo administration

• Change in plasma MR-proANP levels between baseline and 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.

  From baseline (0 minutes) to 60 minutes after diclofenac/placebo administration

• Change in plasma MR-proANP levels between baseline and 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.

  From baseline (0 minutes) to 90 minutes after diclofenac/placebo administration

• Change in plasma MR-proANP levels between baseline and 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.

  From baseline (0 minutes) to 120 minutes after diclofenac/placebo administration

• Change in plasma MR-proANP levels between baseline and 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.

  From baseline (0 minutes) to 240 minutes after diclofenac/placebo administration

Secondary Outcomes (21)

• Change in serum sodium levels between baseline and 15 minutes after diclofenac/placebo administration

  From baseline (0 minutes) to 15 minutes after diclofenac/placebo administration

• Change in serum sodium levels between baseline and 30 minutes after diclofenac/placebo administration

  From baseline (0 minutes) to 30 minutes after diclofenac/placebo administration

• Change in serum sodium levels between baseline and 45 minutes after diclofenac/placebo administration

  From baseline (0 minutes) to 45 minutes after diclofenac/placebo administration

• Change in serum sodium levels between baseline and 60 minutes after diclofenac/placebo administration

  From baseline (0 minutes) to 60 minutes after diclofenac/placebo administration

• Change in serum sodium levels between baseline and 90 minutes after diclofenac/placebo administration

  From baseline (0 minutes) to 90 minutes after diclofenac/placebo administration

Study Arms (2)

Intravenous Infusion of Diclofenac Sodium

EXPERIMENTAL

Intravenous Infusion of Diclofenac Sodium in healthy subjects.

Drug: Intravenous Infusion of Diclofenac Sodium

Intravenous Infusion of Placebo

PLACEBO COMPARATOR

Intravenous Infusion of Placebo (isotonic saline) in healthy subjects.

Drug: Intravenous Infusion of Placebo

Interventions

Intravenous Infusion of Diclofenac Sodium DRUG

Intravenous Infusion of Diclofenac Sodium is administered at the dose of 75 mg, diluted in 100 ml of isotonic saline, over 15 minutes.

Intravenous Infusion of Diclofenac Sodium

Intravenous Infusion of Placebo DRUG

Intravenous Infusion of Placebo (represented by 100 ml of isotonic saline) is administered over 15 minutes.

Intravenous Infusion of Placebo

Eligibility Criteria

• Age: 20 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may not qualify if:

• 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

Sponsors & Collaborators

• A.O.U. Città della Salute e della Scienza: lead

Study Sites (1)

AOU Città della Salute e della Scienza

Turin, Piedmont, 10126, Italy

Location

Related Publications (21)

• Cheung NT, Coley S, Sheeran T, Situnayake RD. Syndrome of inappropriate secretion of antidiuretic hormone induced by diclofenac. BMJ. 1993 Jan 16;306(6871):186. doi: 10.1136/bmj.306.6871.186-a. No abstract available.

  PMID: 8443484 BACKGROUND

• Verrua E, Mantovani G, Ferrante E, Noto A, Sala E, Malchiodi E, Iapichino G, Peccoz PB, Spada A. Severe water intoxication secondary to the concomitant intake of non-steroidal anti-inflammatory drugs and desmopressin: a case report and review of the literature. Hormones (Athens). 2013 Jan-Mar;12(1):135-41. doi: 10.1007/BF03401295.

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• Roche C, Ragot C, Moalic JL, Simon F, Oliver M. Ibuprofen can induce syndrome of inappropriate diuresis in healthy young patients. Case Rep Med. 2013;2013:167267. doi: 10.1155/2013/167267. Epub 2013 Jun 12.

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• Lim SY, Panikkath R, Prabhakar S. Syndrome of inappropriate antidiuretic hormone secretion associated with prolonged keterolac use. Clin Nephrol Case Stud. 2014 Jan 22;2:5-8. doi: 10.5414/CNCS108083. eCollection 2014.

  PMID: 29043122 BACKGROUND

• Spasovski G, Vanholder R, Allolio B, Annane D, Ball S, Bichet D, Decaux G, Fenske W, Hoorn EJ, Ichai C, Joannidis M, Soupart A, Zietse R, Haller M, van der Veer S, Van Biesen W, Nagler E; Hyponatraemia Guideline Development Group. Clinical practice guideline on diagnosis and treatment of hyponatraemia. Eur J Endocrinol. 2014 Feb 25;170(3):G1-47. doi: 10.1530/EJE-13-1020. Print 2014 Mar.

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• Murase T, Tian Y, Fang XY, Verbalis JG. Synergistic effects of nitric oxide and prostaglandins on renal escape from vasopressin-induced antidiuresis. Am J Physiol Regul Integr Comp Physiol. 2003 Feb;284(2):R354-62. doi: 10.1152/ajpregu.00065.2002. Epub 2002 Oct 10.

  PMID: 12388460 BACKGROUND

• Babina AV, Lavrinenko VA, Shestopalova LV, Ivanova LN. Morphological characteristics of the inner medullary zone in the kidneys of Brattleboro and Wistar rats during blockade of prostaglandin synthesis. Bull Exp Biol Med. 2011 Jun;151(2):268-72. doi: 10.1007/s10517-011-1305-0.

  PMID: 22238766 BACKGROUND

• Lavrinenko VA, Babina AV, Shestopalova LV, Beizel NF, Ivanova LN. Effects of sodium diclofenac on the concentration function in animals with different neurohypophyseal status. Bull Exp Biol Med. 2012 Apr;152(6):728-30. doi: 10.1007/s10517-012-1617-8. English, Russian.

  PMID: 22803175 BACKGROUND

• Babina AV, Lavrinenko VA. Electron Microscopic Study of the Inner Medulla in Rat Kidneys under Conditions of Vasopressin Treatment Combined with Prostaglandin Synthesis Blockade. Bull Exp Biol Med. 2016 Oct;161(6):850-852. doi: 10.1007/s10517-016-3527-7. Epub 2016 Oct 25.

  PMID: 27783283 BACKGROUND

• Lavrinenko VA, Babina AV. Efficiency of Osmotic Concentration after Combined Treatment with Vasopressin and Blockage of Prostaglandin Synthesis. Bull Exp Biol Med. 2016 Dec;162(2):187-190. doi: 10.1007/s10517-016-3572-2. Epub 2016 Dec 2.

  PMID: 27909962 BACKGROUND

• Palmer BF, Clegg DJ. Altered Prostaglandin Signaling as a Cause of Thiazide-Induced Hyponatremia. Am J Kidney Dis. 2018 Jun;71(6):769-771. doi: 10.1053/j.ajkd.2017.11.026. Epub 2018 Feb 28. No abstract available.

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• Heida JE, Boesten LSM, Ettema EM, Muller Kobold AC, Franssen CFM, Gansevoort RT, Zittema D. Comparison of ex vivo stability of copeptin and vasopressin. Clin Chem Lab Med. 2017 Jun 27;55(7):984-992. doi: 10.1515/cclm-2016-0559.

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MeSH Terms

Conditions

Hypopituitarism

Condition Hierarchy (Ancestors)

Pituitary Diseases; Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Full Professor

Study Record Dates

• First Submitted: December 1, 2021
• First Posted: January 12, 2022
• Study Start: October 1, 2021
• Primary Completion: December 31, 2021
• Study Completion: December 31, 2021
• Last Updated: January 12, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)