Postoperative PainNCT06724432
Analgesic and Antioxidant Effects of Melatonin in Pediatric Surgery
A study testing oral melatonin in people with Postoperative Pain and Oxidative Stress Response, run by University of Parma at 2 sites in Italy.
Trial summary
Background. Long-term consequences of postoperative pain are detrimental in children. We tested the hypothesis that melatonin reduces postoperative pain and oxidative stress involving sirtuin pathway in children undergoing surgery. Methods. Read more about this study
- Who is it for?
- Ages 3 to 5 years
- Conditions the study is for
- Postoperative Pain, Oxidative Stress Response
- What is being tested?
- oral melatonin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 44 participants
- Where
- 2 sitesItaly
- Study dates
- 1 Jun 2021to 1 Sep 2024
- Phase
- Interventional
- 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 3 to 5 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Children between 3 and 5 years of age scheduled for elective surgery, parental consent
Who cannot join
- Children with cerebral malformations and/or injuries, or surgery in the afternoon or at night to eliminate conditions that could affect melatonin production, or denial of parental consent
Trial locations and contacts
2 sites in 1 country.
Italy2 sites
University Hospital of Messina, Italy
Messina, 98125
Neonatology Unit, Department of Medicine and Surgery, University of Parma, Pietro Barilla Children's Hospital
Parma, 43126
About this study
Official title: Evaluation of Effects of Melatonin in Reducing Postoperative Pain and Oxidative Stress in Children Undergoing Surgery,. Trought Circulating miR-34 and miR-124a, 4-Hydroxynonenal and Sirtuin 1 (SIRT1) Plasma Concentrations.
Background. Long-term consequences of postoperative pain are detrimental in children. We tested the hypothesis that melatonin reduces postoperative pain and oxidative stress involving sirtuin pathway in children undergoing surgery.
Methods. Thirty-one children were randomly assigned to oral supplementation with melatonin or placebo, before surgery. Plasma levels of 4-hydroxynonenal (4-HNE), melatonin, sirtuin 1 (SIRT1), and circulating miR-34 and miR-124a were analyzed at T0 (pre-hospitalization), T1 (before surgery), and T2 (1 h after the end of the surgery).
Read the detailed description
Melatonin shows a potential role in protecting neonates undergoing surgery from the deleterious effects of oxidative stress (OS). After administration of exogenous melatonin, a significant reduction in lipid and protein peroxidation in the postoperative period has been reported in neonates. Recently, Song et al. reported that sirtuin 1 (SIRT1) also plays a critical role in the pathogenesis of pain, showing analgesic effects in chronic pain conditions such as neuropathic and inflammatory pain. In this prospective, randomized, double-blind pilot study, we test the hypothesis that melatonin reduces OS and postoperative pain involving the sirtuin pathway in children undergoing surgery.
Melatonin (Dicoson, Dicofarm, Italy, 5 drops = 1 mg) was administered orally. The product is listed in the Register of Dietary Supplements on the website of the Ministry of Health (http://www.ministerosalute.it/alimenti/dietetica) and is classified with the following code: 943314283. This product is subject to the European Directive on Foodstuffs according to DL n. 169 of May 21, 2004, and not to the European Directive on Medicines 2001/20/EC transposed at the Italian level with D.L. n. 211 of June 24, 2003. Melatonin administration has a good safety profile, with no known adverse effects.
Melatonin plasma levels were assessed at each experimental time point (T0, T1, T2) using a competitive enzyme-linked immunosorbent assay (cELISA) kit from Antibodies.com (A87093) according to the manufacturer's instructions. T1 and T2 plasma samples from Mel treated children suspected of containing concentrations higher than the highest standard (500 pg/mL) were diluted 1:100 (v/v) with sample diluent prior to analysis. Color development was monitored at 450 nm in a Thermo Scientific (MultiSkan FC) microplate reader, and a standard curve (range 7.813-500 pg/mL) was generated using a four-parameter logistic (4-PL) curve fit. The sensitivity of the assay was 4.688 pg/mL; the intra- and inter-assay coefficients of variation were <8% and <10%, respectively.
4-Hydroxynonenal (4-HNE) as a marker of lipid peroxidation was measured to evaluate OS by using a cELISA kit from Antibodies.com (A86962). Plasma concentrations were calculated by reading the absorbance at 450 nm and referring to the standard curve (range 31.25-2000 pg/mL). The sensitivity of the assay was 18.75 pg/mL; the intra- and inter-assay coefficients of variation were <8% and <10%, respectively.
SIRT1 was quantified using an ELISA kit from Invitrogen (EH427RB). Plasma samples were diluted 1:2 as indicated by the Manufacturer before analysis. SIRT1 concentrations were calculated by absorbance reading at 450 nm and referring to the standard curve (range 1.23-300 ng/mL). The sensitivity of the assay was 1.23 ng/mL; the intra- and inter-assay coefficients of variation were <10% and <12%, respectively.
We performed microRNA analyses based on the quali-quantitative plasma sample available (N=3 at each time point, T0, T1, and T2). MicroRNAs (miR-34 and miR-124a) were isolated from plasma using the Norgen total RNA isolation kit13.The Plasma microRNAs and spike-in cel-miR-39 expressions were evaluated using the TaqMan miRNA assay. The TaqMan miRNA reverse transcription kit was used to reverse transcribe miRNAs. Subsequently, RT-qPCR was performed in 20 μL of PCR mix containing 1 μL of 20× TaqMan miRNA assay, which contained PCR primers and probes (5'-FAM), 10 μL of 2×TaqMan Universal PCR Master Mix No Amp Erase UNG and 5 μL of reverse-transcribed product. The reaction was first incubated at 95 °C for 10 min followed by 40 cycles at 95 °C for 15 s and at 60 °C for 1 min. The quantitative real-time PCR (RT-qPCR) was performed on a ABIPRISM 7500 Real Time PCR System. Data was analyzed by a 7500-system software (1 1.4.0) with the automatic comparative threshold (Ct) setting for adapting baseline. Detection thresholds were set at 35 Ct. The relative amounts of miR-34 and miR-124a were calculated using the Ct method: ΔCt = Ct (miR-34/miR-124a) - Ct (refence miRNA); 2-ΔCt.
- Conditions
- Postoperative Pain, Oxidative Stress Response
- Being tested
- oral melatonin, Placebo
- Keywords
- children, surgery, postoperative pain, analgesia, melatonin, 4-hydroxynonenal (4-HNE), sirtuin 1 (SIRT1), miR-34, miR-124a
- Medical subject headings
- Pain, Postoperative, Agnosia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
oral melatoninDrug
Melatonin treated children receive a single dose of oral melatonin 0.5 mg/kg (for a max 10 mg) in a fixed volume of 5 mL of water , 1 hour before induction of anesthesia for surgery
PlaceboDrug
Children in the Control group receive 5 ml of 5% dextrose solution once 1 hour before induction of anesthesia
| Study group | Role | What they receive |
|---|---|---|
| Melatonin arm | Experimental | Mel treated children receive a single dose of oral melatonin 0.5 mg/kg (for a max 10 mg). Melatonin (Dicoson, Dicofarm, Italy) is prepared by a dedicated resident in a fixed volume of 5 mL by adding water to a syringe without a needle. Receives: Drug: oral melatonin |
| Control arm | Placebo comparator | Children in the Control group receive 5 ml of 5% dextrose solution. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma levels evaluation of 4-hydroxynonenal (4-HNE), melatonin, sirtuin 1 (SIRT1), and circulating miR-34 and miR-124a
Melatonin plasma levels were assessed using a competitive enzyme-linked immunosorbent assay (cELISA) kit from Antibodies.com (A87093) according to the manufacturer's instructions.
4-Hydroxynonenal (4-HNE) as a marker of lipid peroxidation was measured to evaluate OS by using a cELISA kit from Antibodies.com (A86962).
SIRT1 was quantified using an ELISA kit from Invitrogen (EH427RB). MicroRNAs (miR-34 and miR-124a) were isolated from plasma using the Norgen total RNA isolation kit13.The Plasma microRNAs and spike-in cel-miR-39 expressions were evaluated using the TaqMan miRNA assay.
Measured: Samples of 0.2 mL of plasma were collected at T0 (pre-hospitalization, 1 day before surgery), T1 (before surgery, pre-anesthesia) and T2 (at 1 h after the end of the surgery and awakening after anesthesia), and biochemical analyses performed.
Secondary outcomes (1)
control post operative pain in children treated with melatonin compared to placebo
doses of paracetamol to control post operative pain were recorded in children treated with melatonin compared to placebo
Measured: 48 hours after surgery were considered as post-operative period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2024
- Study start1 Jun 2021
- Primary completion1 Jun 2023
- Study completion1 Sep 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Postoperative PainStudies 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 N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- children were randomly assigned to oral supplementation with melatonin or placebo (5% dexstrose), before induction of an anesthesia for surgery
- Masking
- Double blind
- Who is masked
- Care provider, Outcomes assessor
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Parma
- Sponsor type
- University, hospital or other
- Collaborators
- University of Messina, University of Florida, University of Siena, University of Urbino "Carlo Bo"
- Responsible party
- Principal investigator, Serafina Perrone, University of Parma
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06724432
- Sponsor's protocol ID
- ethics committee 125222022
- Status last verified
- Dec 2024
- First submitted
- 4 Dec 2024
- Last updated
- 17 Dec 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Effects of Melatonin in Reducing Postoperative Pain and Oxidative Stress in Children Undergoing Surgery,. Trought Circulating miR-34 and miR-124a, 4-Hydroxynonenal and Sirtuin 1 (SIRT1) Plasma Concentrations.
- ClinicalTrials.gov ID
- NCT06724432
- Acronym / sponsor ID
- ethics committee 125222022
- Conditions
- Postoperative Pain, Oxidative Stress Response
- Keywords
- children, surgery, postoperative pain, analgesia, melatonin, 4-hydroxynonenal (4-HNE), sirtuin 1 (SIRT1), miR-34
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- University of ParmaUniversity, hospital or other
- Collaborators
- University of Messina, University of Florida, University of Siena, University of Urbino "Carlo Bo"
- Study start
- 1 Jun 2021 (actual)
- Primary completion
- 1 Jun 2023 (actual)
- Study completion
- 1 Sep 2024 (actual)
- First posted
- 9 Dec 2024 (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.
Background. Long-term consequences of postoperative pain are detrimental in children. We tested the hypothesis that melatonin reduces postoperative pain and oxidative stress involving sirtuin pathway in children undergoing surgery.
Methods. Thirty-one children were randomly assigned to oral supplementation with melatonin or placebo, before surgery. Plasma levels of 4-hydroxynonenal (4-HNE), melatonin, sirtuin 1 (SIRT1), and circulating miR-34 and miR-124a were analyzed at T0 (pre-hospitalization), T1 (before surgery), and T2 (1 h after the end of the surgery).
Detailed description
Melatonin shows a potential role in protecting neonates undergoing surgery from the deleterious effects of oxidative stress (OS). After administration of exogenous melatonin, a significant reduction in lipid and protein peroxidation in the postoperative period has been reported in neonates. Recently, Song et al. reported that sirtuin 1 (SIRT1) also plays a critical role in the pathogenesis of pain, showing analgesic effects in chronic pain conditions such as neuropathic and inflammatory pain. In this prospective, randomized, double-blind pilot study, we test the hypothesis that melatonin reduces OS and postoperative pain involving the sirtuin pathway in children undergoing surgery.
Melatonin (Dicoson, Dicofarm, Italy, 5 drops = 1 mg) was administered orally. The product is listed in the Register of Dietary Supplements on the website of the Ministry of Health (http://www.ministerosalute.it/alimenti/dietetica) and is classified with the following code: 943314283. This product is subject to the European Directive on Foodstuffs according to DL n. 169 of May 21, 2004, and not to the European Directive on Medicines 2001/20/EC transposed at the Italian level with D.L. n. 211 of June 24, 2003. Melatonin administration has a good safety profile, with no known adverse effects.
Melatonin plasma levels were assessed at each experimental time point (T0, T1, T2) using a competitive enzyme-linked immunosorbent assay (cELISA) kit from Antibodies.com (A87093) according to the manufacturer's instructions. T1 and T2 plasma samples from Mel treated children suspected of containing concentrations higher than the highest standard (500 pg/mL) were diluted 1:100 (v/v) with sample diluent prior to analysis. Color development was monitored at 450 nm in a Thermo Scientific (MultiSkan FC) microplate reader, and a standard curve (range 7.813-500 pg/mL) was generated using a four-parameter logistic (4-PL) curve fit. The sensitivity of the assay was 4.688 pg/mL; the intra- and inter-assay coefficients of variation were <8% and <10%, respectively.
4-Hydroxynonenal (4-HNE) as a marker of lipid peroxidation was measured to evaluate OS by using a cELISA kit from Antibodies.com (A86962). Plasma concentrations were calculated by reading the absorbance at 450 nm and referring to the standard curve (range 31.25-2000 pg/mL). The sensitivity of the assay was 18.75 pg/mL; the intra- and inter-assay coefficients of variation were <8% and <10%, respectively.
SIRT1 was quantified using an ELISA kit from Invitrogen (EH427RB). Plasma samples were diluted 1:2 as indicated by the Manufacturer before analysis. SIRT1 concentrations were calculated by absorbance reading at 450 nm and referring to the standard curve (range 1.23-300 ng/mL). The sensitivity of the assay was 1.23 ng/mL; the intra- and inter-assay coefficients of variation were <10% and <12%, respectively.
We performed microRNA analyses based on the quali-quantitative plasma sample available (N=3 at each time point, T0, T1, and T2). MicroRNAs (miR-34 and miR-124a) were isolated from plasma using the Norgen total RNA isolation kit13.The Plasma microRNAs and spike-in cel-miR-39 expressions were evaluated using the TaqMan miRNA assay. The TaqMan miRNA reverse transcription kit was used to reverse transcribe miRNAs. Subsequently, RT-qPCR was performed in 20 μL of PCR mix containing 1 μL of 20× TaqMan miRNA assay, which contained PCR primers and probes (5'-FAM), 10 μL of 2×TaqMan Universal PCR Master Mix No Amp Erase UNG and 5 μL of reverse-transcribed product. The reaction was first incubated at 95 °C for 10 min followed by 40 cycles at 95 °C for 15 s and at 60 °C for 1 min. The quantitative real-time PCR (RT-qPCR) was performed on a ABIPRISM 7500 Real Time PCR System. Data was analyzed by a 7500-system software (1 1.4.0) with the automatic comparative threshold (Ct) setting for adapting baseline. Detection thresholds were set at 35 Ct. The relative amounts of miR-34 and miR-124a were calculated using the Ct method: ΔCt = Ct (miR-34/miR-124a) - Ct (refence miRNA); 2-ΔCt.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (care provider, outcomes assessor)
- Number of arms
- 2
- Model description
- children were randomly assigned to oral supplementation with melatonin or placebo (5% dexstrose), before induction of an anesthesia for surgery
| Arm | Type | Receives |
|---|---|---|
| Melatonin arm | Experimental | Drug: oral melatoninMel treated children receive a single dose of oral melatonin 0.5 mg/kg (for a max 10 mg). Melatonin (Dicoson, Dicofarm, Italy) is prepared by a dedicated resident in a fixed volume of 5 mL by adding water to a syringe without a needle. |
| Control arm | Placebo comparator | Drug: PlaceboChildren in the Control group receive 5 ml of 5% dextrose solution. |
Who may qualify
- Ages
- 3 to 5 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (1 listed)
- Children between 3 and 5 years of age scheduled for elective surgery, parental consent
Key exclusion criteria (1 listed)
- Children with cerebral malformations and/or injuries, or surgery in the afternoon or at night to eliminate conditions that could affect melatonin production, or denial of parental consent
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 |
|---|---|---|
| oral melatoninMelatonin treated children receive a single dose of oral melatonin 0.5 mg/kg (for a max 10 mg) in a fixed volume of 5 mL of water , 1 hour before induction of anesthesia for surgery | Drug | Melatonin arm |
| PlaceboChildren in the Control group receive 5 ml of 5% dextrose solution once 1 hour before induction of anesthesia | Drug | Control arm |
Primary outcome
Plasma levels evaluation of 4-hydroxynonenal (4-HNE), melatonin, sirtuin 1 (SIRT1), and circulating miR-34 and miR-124a
Time frame: Samples of 0.2 mL of plasma were collected at T0 (pre-hospitalization, 1 day before surgery), T1 (before surgery, pre-anesthesia) and T2 (at 1 h after the end of the surgery and awakening after anesthesia), and biochemical analyses performed.
Melatonin plasma levels were assessed using a competitive enzyme-linked immunosorbent assay (cELISA) kit from Antibodies.com (A87093) according to the manufacturer's instructions. 4-Hydroxynonenal (4-HNE) as a marker of lipid peroxidation was measured to evaluate OS by using a cELISA kit from Antibodies.com (A86962). SIRT1 was quantified using an ELISA kit from Invitrogen (EH427RB). MicroRNAs (miR-34 and miR-124a) were isolated from plasma using the Norgen total RNA isolation kit13.The Plasma microRNAs and spike-in cel-miR-39 expressions were evaluated using the TaqMan miRNA assay.
1 secondary outcome
control post operative pain in children treated with melatonin compared to placebo
Time frame: 48 hours after surgery were considered as post-operative period
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 17 Dec 2024.
- 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.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing oral melatonin in people with Postoperative Pain and Oxidative Stress Response, run by University of Parma at 2 sites 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 1 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 17 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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.
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?
Plasma levels evaluation of 4-hydroxynonenal (4-HNE), melatonin, sirtuin 1 (SIRT1), and circulating miR-34 and miR-124a (time frame: Samples of 0.2 mL of plasma were collected at T0 (pre-hospitalization, 1 day before surgery), T1 (before surgery, pre-anesthesia) and T2 (at 1 h after the end of the surgery and awakening after anesthesia), and biochemical analyses performed.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 17 Dec 2024; AzTrials last refreshed its copy on 8 Nov 2026.