HypopituitarismPhase 4NCT05188131
Acute Neuroendocrine Response to Intravenous Infusion of Diclofenac Sodium
A Phase 4 study testing Intravenous Infusion of Diclofenac Sodium in people with Hypopituitarism, run by A.O.U. Città della Salute e della Scienza at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Hypopituitarism
- What is being tested?
- Intravenous Infusion of Diclofenac Sodium
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 1 siteItaly
- Study dates
- 1 Oct 2021to 31 Dec 2021
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Any adult healthy subject (with age 20-50 years old) not meeting any of the exclusion criteria listed below
Who cannot join
- 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
Show all 12Show fewer
- History of gastrointestinal bleeding
- History of kidney disease
- History of heart disease
- History of asthma
- Known allergy to NSAIDs
- Any current acute medical condition
Trial locations and contacts
1 site in 1 country.
About this study
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
- Being tested
- Intravenous Infusion of Diclofenac Sodium, Intravenous Infusion of Placebo
- Medical subject headings
- Hypopituitarism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intravenous Infusion of Diclofenac SodiumDrug
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 PlaceboDrug
Intravenous Infusion of Placebo (represented by 100 ml of isotonic saline) is administered over 15 minutes.
| Study group | Role | What they receive |
|---|---|---|
| Intravenous Infusion of Diclofenac Sodium | Experimental | Intravenous Infusion of Diclofenac Sodium in healthy subjects. Receives: Drug: Intravenous Infusion of Diclofenac Sodium |
| Intravenous Infusion of Placebo | Placebo comparator | Intravenous Infusion of Placebo (isotonic saline) in healthy subjects. Receives: Drug: Intravenous Infusion of Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: From baseline (0 minutes) to 90 minutes after diclofenac/placebo administration
Change in serum sodium levels between baseline and 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.
Measured: From baseline (0 minutes) to 120 minutes after diclofenac/placebo administration
Change in serum sodium levels between baseline and 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.
Measured: From baseline (0 minutes) to 240 minutes after diclofenac/placebo administration
Change in plasma MR-proADM levels between baseline and 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.
Measured: From baseline (0 minutes) to 15 minutes after diclofenac/placebo administration
Change in plasma MR-proADM levels between baseline and 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.
Measured: From baseline (0 minutes) to 30 minutes after diclofenac/placebo administration
Change in plasma MR-proADM levels between baseline and 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.
Measured: From baseline (0 minutes) to 45 minutes after diclofenac/placebo administration
Change in plasma MR-proADM levels between baseline and 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.
Measured: From baseline (0 minutes) to 60 minutes after diclofenac/placebo administration
Change in plasma MR-proADM levels between baseline and 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.
Measured: From baseline (0 minutes) to 90 minutes after diclofenac/placebo administration
Change in plasma MR-proADM levels between baseline and 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.
Measured: From baseline (0 minutes) to 120 minutes after diclofenac/placebo administration
Change in plasma MR-proADM levels between baseline and 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.
Measured: From baseline (0 minutes) to 240 minutes after diclofenac/placebo administration
Change in urine sodium levels between baseline and 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.
Measured: From baseline (0 minutes) to 240 minutes after diclofenac/placebo administration
Change in urine potassium levels between baseline and 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.
Measured: From baseline (0 minutes) to 240 minutes after diclofenac/placebo administration
Change in urine osmolality between baseline and 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.
Measured: From baseline (0 minutes) to 240 minutes after diclofenac/placebo administration
Change in resistance at bioimpedance vector analysis between baseline and 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.
Measured: From baseline (0 minutes) to 240 minutes after diclofenac/placebo administration
Change in reactance at bioimpedance vector analysis between baseline and 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.
Measured: From baseline (0 minutes) to 240 minutes after diclofenac/placebo administration
Change in phase angle at bioimpedance vector analysis between baseline and 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.
Measured: From baseline (0 minutes) to 240 minutes after diclofenac/placebo administration
Change in late-night salivary cortisol levels between 9 hours before and 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.
Measured: From 9 hours before to 15 hours after diclofenac/placebo administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jan 2022
- Study start1 Oct 2021
- Primary completion31 Dec 2021
- Study completion31 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (21)Papers the sponsor has linked to this study.
- Other trials for HypopituitarismStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- A.O.U. Città della Salute e della Scienza
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ezio Ghigo, A.O.U. Città della Salute e della Scienza
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05188131
- Sponsor's protocol ID
- NR-DICLO
- Status last verified
- Jan 2022
- First submitted
- 1 Dec 2021
- Last updated
- 12 Jan 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 8443484Verrua 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.
PubMed 23624139Roche 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.
PubMed 23840216Lim 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.
PubMed 29043122Spasovski 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.
PubMed 24569125Murase 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.
PubMed 12388460Babina 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.
PubMed 22238766Lavrinenko 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.
PubMed 22803175Babina 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.
PubMed 27783283Lavrinenko 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.
PubMed 27909962Palmer 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.
PubMed 29501264Puurunen J, Leppaluoto J. Centrally administered PGE2 inhibits gastric secretion in the rat by releasing vasopressin. Eur J Pharmacol. 1984 Sep 3;104(1-2):145-50. doi: 10.1016/0014-2999(84)90381-9.
PubMed 6094207Bojanowska E, Guzek JW. Inhibition of prostaglandin synthesis and the release of vasopressin and oxytocin from the rat neurohypophysis: in vitro studies. Exp Clin Endocrinol. 1991;98(3):213-21. doi: 10.1055/s-0029-1211120.
PubMed 1778241Walker BR. Suppressed basal antidiuretic hormone release during cyclooxygenase inhibition in conscious dogs. Am J Physiol. 1983 Apr;244(4):R487-91. doi: 10.1152/ajpregu.1983.244.4.R487.
PubMed 6404183Heida 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.
PubMed 27879483
Study at a glance
From the registry record, last updated by the sponsor on 12 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Acute Neuroendocrine Response to Intravenous Infusion of Diclofenac Sodium
- ClinicalTrials.gov ID
- NCT05188131
- Acronym / sponsor ID
- NR-DICLO
- Conditions
- Hypopituitarism
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- A.O.U. Città della Salute e della ScienzaUniversity, hospital or other
- Study start
- 1 Oct 2021 (actual)
- Primary completion
- 31 Dec 2021 (actual)
- Study completion
- 31 Dec 2021 (actual)
- First posted
- 12 Jan 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intravenous Infusion of Diclofenac Sodium | Experimental | Drug: Intravenous Infusion of Diclofenac SodiumIntravenous Infusion of Diclofenac Sodium in healthy subjects. |
| Intravenous Infusion of Placebo | Placebo comparator | Drug: Intravenous Infusion of PlaceboIntravenous Infusion of Placebo (isotonic saline) in healthy subjects. |
Who may qualify
- Ages
- 20 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Any adult healthy subject (with age 20-50 years old) not meeting any of the exclusion criteria listed below
Key exclusion criteria (12 listed)
- BMI < 18.5 kg/m2 or > 25 kg/m2
- Any active pharmacological treatment
- Pregnancy or breastfeeding
- History of polyuria/polydipsia syndrome
- History of dysionia
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intravenous Infusion of Diclofenac SodiumIntravenous Infusion of Diclofenac Sodium is administered at the dose of 75 mg, diluted in 100 ml of isotonic saline, over 15 minutes. | Drug | Intravenous Infusion of Diclofenac Sodium |
| Intravenous Infusion of PlaceboIntravenous Infusion of Placebo (represented by 100 ml of isotonic saline) is administered over 15 minutes. | Drug | Intravenous Infusion of Placebo |
Primary outcome
Change in plasma copeptin levels between baseline and 15 minutes after diclofenac/placebo administration
Time frame: From 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 administration
Time frame: From 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 45 minutes after diclofenac/placebo administration
Time frame: From 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 60 minutes after diclofenac/placebo administration
Time frame: From 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 copeptin levels between baseline and 90 minutes after diclofenac/placebo administration
Time frame: From 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 120 minutes after diclofenac/placebo administration
Time frame: From 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 copeptin levels between baseline and 240 minutes after diclofenac/placebo administration
Time frame: From 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 administration
Time frame: From 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 30 minutes after diclofenac/placebo administration
Time frame: From 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 MR-proANP levels between baseline and 45 minutes after diclofenac/placebo administration
Time frame: From 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 60 minutes after diclofenac/placebo administration
Time frame: From 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 MR-proANP levels between baseline and 90 minutes after diclofenac/placebo administration
Time frame: From 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 120 minutes after diclofenac/placebo administration
Time frame: From 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 240 minutes after diclofenac/placebo administration
Time frame: From 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.
21 secondary outcomes
Change in serum sodium levels between baseline and 15 minutes after diclofenac/placebo administration
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: From baseline (0 minutes) to 90 minutes after diclofenac/placebo administration
Change in serum sodium levels between baseline and 120 minutes after diclofenac/placebo administration
Time frame: From baseline (0 minutes) to 120 minutes after diclofenac/placebo administration
Change in serum sodium levels between baseline and 240 minutes after diclofenac/placebo administration
Time frame: From baseline (0 minutes) to 240 minutes after diclofenac/placebo administration
Change in plasma MR-proADM levels between baseline and 15 minutes after diclofenac/placebo administration
Time frame: From baseline (0 minutes) to 15 minutes after diclofenac/placebo administration
Change in plasma MR-proADM levels between baseline and 30 minutes after diclofenac/placebo administration
Time frame: From baseline (0 minutes) to 30 minutes after diclofenac/placebo administration
Change in plasma MR-proADM levels between baseline and 45 minutes after diclofenac/placebo administration
Time frame: From baseline (0 minutes) to 45 minutes after diclofenac/placebo administration
Change in plasma MR-proADM levels between baseline and 60 minutes after diclofenac/placebo administration
Time frame: From baseline (0 minutes) to 60 minutes after diclofenac/placebo administration
Change in plasma MR-proADM levels between baseline and 90 minutes after diclofenac/placebo administration
Time frame: From baseline (0 minutes) to 90 minutes after diclofenac/placebo administration
Change in plasma MR-proADM levels between baseline and 120 minutes after diclofenac/placebo administration
Time frame: From baseline (0 minutes) to 120 minutes after diclofenac/placebo administration
Change in plasma MR-proADM levels between baseline and 240 minutes after diclofenac/placebo administration
Time frame: From baseline (0 minutes) to 240 minutes after diclofenac/placebo administration
Change in urine sodium levels between baseline and 240 minutes after diclofenac/placebo administration
Time frame: From baseline (0 minutes) to 240 minutes after diclofenac/placebo administration
Change in urine potassium levels between baseline and 240 minutes after diclofenac/placebo administration
Time frame: From baseline (0 minutes) to 240 minutes after diclofenac/placebo administration
Change in urine osmolality between baseline and 240 minutes after diclofenac/placebo administration
Time frame: From baseline (0 minutes) to 240 minutes after diclofenac/placebo administration
Change in resistance at bioimpedance vector analysis between baseline and 240 minutes after diclofenac/placebo administration
Time frame: From baseline (0 minutes) to 240 minutes after diclofenac/placebo administration
Change in reactance at bioimpedance vector analysis between baseline and 240 minutes after diclofenac/placebo administration
Time frame: From baseline (0 minutes) to 240 minutes after diclofenac/placebo administration
Change in phase angle at bioimpedance vector analysis between baseline and 240 minutes after diclofenac/placebo administration
Time frame: From baseline (0 minutes) to 240 minutes after diclofenac/placebo administration
Change in late-night salivary cortisol levels between 9 hours before and 15 hours after diclofenac/placebo administration
Time frame: From 9 hours before to 15 hours after diclofenac/placebo administration
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jan 2022.
- Background: PubMed 8443484Cheung 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.
- Background: PubMed 23624139Verrua 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.
- Background: PubMed 23840216Roche 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.
- Background: PubMed 29043122Lim 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.
- Background: PubMed 24569125Spasovski 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.
- Background: PubMed 12388460Murase 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.
- Background: PubMed 22238766Babina 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.
- Background: PubMed 22803175Lavrinenko 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.
- Background: PubMed 27783283Babina 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.
- Background: PubMed 27909962Lavrinenko 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.
- Background: PubMed 29501264Palmer 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.
- Background: PubMed 6094207Puurunen J, Leppaluoto J. Centrally administered PGE2 inhibits gastric secretion in the rat by releasing vasopressin. Eur J Pharmacol. 1984 Sep 3;104(1-2):145-50. doi: 10.1016/0014-2999(84)90381-9.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Intravenous Infusion of Diclofenac Sodium in people with Hypopituitarism, run by A.O.U. Città della Salute e della Scienza at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in plasma copeptin levels between baseline and 15 minutes after diclofenac/placebo administration (time frame: From baseline (0 minutes) to 15 minutes after diclofenac/placebo administration). The study lists 14 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05188131, which also lists 21 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jan 2022.