Evidence of Liver TransplantationPhase 3NCT01860716
Impact of Melatonin in the Pretreatment of Organ Donor and the Influence in the Evolution of Liver Transplant.
A Phase 3 study testing Melatonin in people with Evidence of Liver Transplantation, run by Aragon Institute of Health Sciences at 1 site in Spain.
Trial summary
Impact of melatonin on organ donor pretreatment and liver transplant recipient: prospective, randomized, double-blind trial. OBJECTIVES. To establish the efficacy of the melatonin administered to encephalic death donors (EDD) in liver transplantation. Read more about this study
- Who is it for?
- Ages 18 to 68 years
- Conditions the study is for
- Evidence of Liver Transplantation
- What is being tested?
- 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
- 60 participants
- Where
- 1 siteSpain
- Study dates
- May 2013to Dec 2013
- Phase
- Phase 3
- 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 18 to 68 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Donors
- Encephalic-death (ED) organ donor who is situated in the ICUs of accredited hospitals in Zaragoza and meets each and every one of the following criteria.
- Being 16 years old or older.
- Informed consent for the donation signed by the immediate family.
- Informed consent for inclusion of the donor in the study .
- Receive intensive treatment and standard maintenance of the donor in ED, in accordance with universally accepted protocols of the Organizacion Nacional de Trasplantes (ONT), of the Aragon Autonomous Transplant Coordination, and of the ICUs and the participating hospitals in the study.
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- Liver transplant recipients
- Being 18 years old or older and being less than 68 years of age.
- Informed consent for the procedure of LT signed.
- Informed consent for patient inclusion in the study, signed the same day that consent to the LT.
Who cannot join
- Donors
- A potential encephalic-death organ donor will not be included in the study if either of the following criteria:
- Absence of either signed informed consent: for organ donation or for inclusion in the study.
- No standard concomitant treatment and management of donor in ED.
- Liver transplant recipients
- Absence of either signed informed consent: for liver transplantation or for inclusion in the study.
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- Split, domino or multiorgan transplantation.
- Grafts removed by other surgical teams.
- Pregnant women or fertile not using contraceptive measures highly effective.
Trial locations and contacts
1 site in 1 country.
Spain1 site
Hospital Clínico Universitario Lozano Blesa
Zaragoza, Zaragoza, 50009
Francisco A. García-Gil, Physician, 0034976765700, agarciagil@telefonica.net
Francisco A. García-Gil, Physician
About this study
Official title: Impact of Melatonin in the Pretreatment of Organ Donor and the Influence in the Evolution of Liver Transplant: a Prospective, Randomised Double-blind Study.
Impact of melatonin on organ donor pretreatment and liver transplant recipient: prospective, randomized, double-blind trial.
OBJECTIVES. To establish the efficacy of the melatonin administered to encephalic death donors (EDD) in liver transplantation. The aim is to improve the functional quality of the retrieved organs, attenuate lesions and ischemia-reperfusion mediators, and provide grafts with greater resistance to post-transplant aggression.
METHODOLOGY. Prospective, randomized, double-blind, pilot trial to evaluate preconditioning with melatonin versus placebo in EDDs. Two groups, melatonin and control-placebo, n=30 per group. Administration to donor via NG tube of 30mg of melatonin or placebo (lactose) upon inclusion in the trial, 60 minutes prior to commencement of surgery and following laparotomy during extraction. Evaluation of response to treatment: A) Conventional clinical, hemodynamic, analytical and histopathological parameters in donor and recipient. B) Plasma determinations for: oxidative/nitrosative stress; acute phase proteins; cellular and humoral immunity; NT-proBNP and cystatin C; endocrine profile; melatonin levels. C) Determinations in liver tissue: quantification of malonyldialdehyde-4hydroxyalkenals and protein carbonyl content; cellular and mitochondrial membrane fluidity; markers of tissue-vascular damage and proliferation: transforming growth factor-beta (TGF-β); hypoxia-inducible factor (HIF) and vascular endothelial growth factor (VEGF). Data will be analyzed following a prospectively define plan and by intention-to-treat analysis.
Read the detailed description
This study will be done in the Hospital Clinico Lozano Blesa (Zaragoza, Spain), promoted by the Health Science Aragon Institute and its principal investigator is F. Agustín García Gil (Surgical Service). It will start in April-May 2013 and will finish 12 months later approximately. The study sponsor is I+CS (Aragon Institute of Health Sciences).
- Conditions
- Evidence of Liver Transplantation
- Being tested
- Melatonin, Placebo
- Keywords
- Melatonin, liver transplant, oxidative stress
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MelatoninDrug
Also called Circadin (Neurim Pharmaceuticals)
Melatonin 2 mg prolonged-release tablet, administration via nasogastric tube.
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Solution for infusion | Placebo comparator | Solution for infusion administrated via nasogastric tube Receives: Drug: Placebo |
| Melatonin | Experimental | 30 mg melatonin administrated via nasogastric tube in the Intensive Care Unit when included in the study and 30 mg melatonin 60 minutes before transfer to the operating room. Receives: Drug: Melatonin |
What is being measured
The primary outcome is the main question the study is designed to answer.
AST levels
Aspartate transaminase (AST) levels will be measured.
Measured: Between days 1 and 10 postoperatively.
ALT
Alanine transaminase (ALT) levels will be measured.
Measured: Between days 1 and 10 postoperatively
Bilirubin levels
Bilirubin levels will be measured.
Measured: Between days 1 and 10 postoperatively
Prothrombin levels
Prothrombin levels will be measured.
Measured: Between days 1 and 10 postoperatively
Secondary outcomes (6)
Post-reperfusion syndrome
Post-reperfusion syndrome
Measured: Transplant day
No primary function and primary graft dysfunction
No primary function and primary graft dysfunction
Measured: Transplant day
Survival of the graft
Survival of the graft
Measured: From day 0 to 3 months
Patient survival
Patient survival
Measured: Day 0 to 3 months
Donor and recipient serological parameters
Donor and recipient serological parameters
Measured: Between days 1 and 10 postoperatively
Morphological and functional quality of the liver graft evaluated by histological parameters of ischemia-reperfusion and tissue biochemical markers
Morphological and functional quality of the liver graft evaluated by histological parameters of ischemia-reperfusion and tissue biochemical markers
Measured: Day 0 and day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 May 2013 (estimated)
- Study startMay 2013
- Primary completionDec 2013 (estimated)
- Study completionDec 2013 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Evidence of Liver TransplantationStudies 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 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Aragon Institute of Health Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- Fondo de Investigacion Sanitaria
- Responsible party
- Sponsor
- Investigators
- Francisco A. García-Gil, Physician, Principal investigator, Hospital Clínico Universitario Lozano Blesa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01860716
- Sponsor's protocol ID
- PI10/02877
- Status last verified
- May 2013
- First submitted
- 17 May 2013
- Last updated
- 23 May 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 23 May 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Melatonin in the Pretreatment of Organ Donor and the Influence in the Evolution of Liver Transplant: a Prospective, Randomised Double-blind Study.
- ClinicalTrials.gov ID
- NCT01860716
- Acronym / sponsor ID
- PI10/02877
- Conditions
- Evidence of Liver Transplantation
- Keywords
- Melatonin, liver transplant, oxidative stress
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Aragon Institute of Health SciencesUniversity, hospital or other
- Collaborators
- Fondo de Investigacion Sanitaria
- Study start
- May 2013
- Primary completion
- Dec 2013 (estimated)
- Study completion
- Dec 2013 (estimated)
- First posted
- 23 May 2013 (estimated)
- 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.
Impact of melatonin on organ donor pretreatment and liver transplant recipient: prospective, randomized, double-blind trial.
OBJECTIVES. To establish the efficacy of the melatonin administered to encephalic death donors (EDD) in liver transplantation. The aim is to improve the functional quality of the retrieved organs, attenuate lesions and ischemia-reperfusion mediators, and provide grafts with greater resistance to post-transplant aggression.
METHODOLOGY. Prospective, randomized, double-blind, pilot trial to evaluate preconditioning with melatonin versus placebo in EDDs. Two groups, melatonin and control-placebo, n=30 per group. Administration to donor via NG tube of 30mg of melatonin or placebo (lactose) upon inclusion in the trial, 60 minutes prior to commencement of surgery and following laparotomy during extraction. Evaluation of response to treatment: A) Conventional clinical, hemodynamic, analytical and histopathological parameters in donor and recipient. B) Plasma determinations for: oxidative/nitrosative stress; acute phase proteins; cellular and humoral immunity; NT-proBNP and cystatin C; endocrine profile; melatonin levels. C) Determinations in liver tissue: quantification of malonyldialdehyde-4hydroxyalkenals and protein carbonyl content; cellular and mitochondrial membrane fluidity; markers of tissue-vascular damage and proliferation: transforming growth factor-beta (TGF-β); hypoxia-inducible factor (HIF) and vascular endothelial growth factor (VEGF). Data will be analyzed following a prospectively define plan and by intention-to-treat analysis.
Detailed description
This study will be done in the Hospital Clinico Lozano Blesa (Zaragoza, Spain), promoted by the Health Science Aragon Institute and its principal investigator is F. Agustín García Gil (Surgical Service). It will start in April-May 2013 and will finish 12 months later approximately. The study sponsor is I+CS (Aragon Institute of Health Sciences).
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Solution for infusion | Placebo comparator | Drug: PlaceboSolution for infusion administrated via nasogastric tube |
| Melatonin | Experimental | Drug: Melatonin30 mg melatonin administrated via nasogastric tube in the Intensive Care Unit when included in the study and 30 mg melatonin 60 minutes before transfer to the operating room. |
Who may qualify
- Ages
- 18 to 68 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Donors
- Encephalic-death (ED) organ donor who is situated in the ICUs of accredited hospitals in Zaragoza and meets each and every one of the following criteria.
- Being 16 years old or older.
- Informed consent for the donation signed by the immediate family.
- Informed consent for inclusion of the donor in the study .
Key exclusion criteria (9 listed)
- Donors
- A potential encephalic-death organ donor will not be included in the study if either of the following criteria:
- Absence of either signed informed consent: for organ donation or for inclusion in the study.
- No standard concomitant treatment and management of donor in ED.
- Liver transplant recipients
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 |
|---|---|---|
| MelatoninAlso: Circadin (Neurim Pharmaceuticals)Melatonin 2 mg prolonged-release tablet, administration via nasogastric tube. | Drug | Melatonin |
| Placebo | Drug | Solution for infusion |
Primary outcome
AST levels
Time frame: Between days 1 and 10 postoperatively.
Aspartate transaminase (AST) levels will be measured.
ALT
Time frame: Between days 1 and 10 postoperatively
Alanine transaminase (ALT) levels will be measured.
Bilirubin levels
Time frame: Between days 1 and 10 postoperatively
Bilirubin levels will be measured.
Prothrombin levels
Time frame: Between days 1 and 10 postoperatively
Prothrombin levels will be measured.
6 secondary outcomes
Post-reperfusion syndrome
Time frame: Transplant day
No primary function and primary graft dysfunction
Time frame: Transplant day
Survival of the graft
Time frame: From day 0 to 3 months
Patient survival
Time frame: Day 0 to 3 months
Donor and recipient serological parameters
Time frame: Between days 1 and 10 postoperatively
Morphological and functional quality of the liver graft evaluated by histological parameters of ischemia-reperfusion and tissue biochemical markers
Time frame: Day 0 and day 1
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 May 2013.
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.
Francisco A. García-Gil, Physician principal investigator
Hospital Clínico Universitario Lozano Blesa
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Melatonin in people with Evidence of Liver Transplantation, run by Aragon Institute of Health Sciences at 1 site in Spain.
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 10 inclusion and 9 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: status not confirmed, as of the sponsor's last update on 23 May 2013. 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 Spain. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
AST levels (time frame: Between days 1 and 10 postoperatively.). The study lists 4 primary outcomes in all. 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 23 May 2013.