Back to resultsDose Assessment of Melatonin in Sepsis Trial (DAMSEL2)
Primary Purpose
Sepsis
Status
Withdrawn
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
Melatonin
Sponsored by
About this trial
This is an interventional treatment trial for Sepsis focused on measuring sepsis, antioxidant, melatonin, inflammation
Eligibility Criteria
Inclusion Criteria:
Adult patients (16 years or over) on the ICU at Aberdeen Royal Infirmary with sepsis due to community acquired pneumonia who are within 24h of fulfilling the criteria for sepsis with clinical suspicion of pneumonia and the presence of chest X-ray changes consistent with pneumonia will be recruited. The criteria for sepsis are:
- clinical suspicion or evidence of acute infection
systemic inflammatory response syndrome, defined by two or more of the following:
- Core temperature <36 or >38°C;
- tachycardia: heart rate > 90 beats/min;
- tachypnoea: respiratory rate > 20 breaths/min or ventilated;
- leucocyte count >12 x 109/L or <4 x 109/L.
Exclusion Criteria:
- <16 years old,
- have a life expectancy <24h,
- have metastatic cancer or immunosuppression,
- are receiving steroids (>20mg/d prednisolone or equivalent, used regularly for >2 weeks prior to ICU admission)
- women of child bearing potential without a negative pregnancy test or a history of surgical sterilization.
- patients receiving fluvoxamine or nifedipine,
- have overt hepatic failure
- unable to tolerate oral medication
- known to be hypersensitive to trial medication and/or excipients
Sites / Locations
- Aberdeen Royal Infirmary
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Melatonin
Placebo
Arm Description
Melatonin at a dose of either 50mg (50ml) or 100mg (100ml) to be decided after an initial PK study to be given at intervals to be decided after PK data is available, for 72h. Oral liquid via nasogastric tube.
Placebo at a dose of either 50ml or 100ml (to be decided after an initial PK study) to be given at intervals to be decided after PK data, is available for 72h. Oral liquid via nasogastric tube.
Outcomes
Primary Outcome Measures
Completion of enrollment of 10 patients to Stage 1
Stage 1= first 5 patients 50mg, second 5 patients 100mg oral melatonin liquid, open label
Secondary Outcome Measures
Composite pharmacokinetic measures for each dose in Stage 1 (T max, CMax and AUC)
T max, CMax and AUC of melatonin and 6-hydroxymelatonin sulphate levels at two doses of melatonin.
Composite biomarker measures in Stage 2 ( linear discriminant analysis, hierarchical regression and hierarchical cluster analysis)
Multiplex biomarker analysis will be used; linear discriminant analysis, hierarchical regression and hierarchical cluster analysis will be used to explore relationships between biomarkers
28d all cause mortality in Stage 2
Survival status at 28d
Arterial blood lactate (stage 1 and stage 2)
Absolute arterial lactate measures at various time points; change over time.
Full Information
NCT ID
NCT02319265
First Posted
December 3, 2014
Last Updated
April 20, 2017
Sponsor
University of Aberdeen
1. Study Identification
Unique Protocol Identification Number
NCT02319265
Brief Title
Dose Assessment of Melatonin in Sepsis Trial
Acronym
DAMSEL2
Official Title
Dose Assessment of Melatonin in Sepsis Trial
Study Type
Interventional
2. Study Status
Record Verification Date
April 2017
Overall Recruitment Status
Withdrawn
Why Stopped
Study registered elsewhere and is not covered by FDA
Study Start Date
April 2017 (Anticipated)
Primary Completion Date
June 2019 (Anticipated)
Study Completion Date
December 2019 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Aberdeen
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
DAMSEL 2 is a pilot Phase II study in patients with sepsis. Stage 1 will assess the pharmacokinetics of melatonin and its major metabolite after a single dose of 50 or 100mg exogenous melatonin in two small groups of patients with sepsis in order to make dosing and dosing interval decisions for Stage 2.
Stage 2 is a double blind randomised controlled trial of melatonin in patients with sepsis at the dose and dosing interval decided after Stage 1. Measurements of melatonin and its major metabolite, and an array of biomarkers of inflammation and oxidative stress will be made, plus transcriptome (mRNA) analysis. This study will inform a planned larger phase II trial.
Detailed Description
Antioxidant therapy targeted at mitochondria has the potential to reduce inflammation, mitochondrial damage and organ dysfunction in sepsis. Melatonin accumulates in mitochondria and both it and its metabolites have potent antioxidant and anti-inflammatory activity, preventing organ dysfunction in a rat model of sepsis. In a recent Phase I dose escalation study (DAMSEL 1) the investigators showed that oral doses of melatonin in healthy subjects were well tolerated with no adverse events and resulted in levels of circulating melatonin and its major metabolite which had beneficial anti-inflammatory and antioxidant actions in ex vivo studiesStage 1 will assess the pharmacokinetics of melatonin and its major metabolite after a single dose of 50 or 100mg exogenous melatonin in two small groups of patients with sepsis in order to make dosing and dosing interval decisions for Stage 2.
Stage 2 is a double blind randomised controlled trial of melatonin in patients with sepsis at the dose and dosing interval decided after Stage 1. Measurements of melatonin and its major metabolite, and an array of biomarkers of inflammation and oxidative stress will be made, plus transcriptome (mRNA) analysis. This study will inform a planned larger phase II trial.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sepsis
Keywords
sepsis, antioxidant, melatonin, inflammation
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Melatonin
Arm Type
Experimental
Arm Description
Melatonin at a dose of either 50mg (50ml) or 100mg (100ml) to be decided after an initial PK study to be given at intervals to be decided after PK data is available, for 72h. Oral liquid via nasogastric tube.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo at a dose of either 50ml or 100ml (to be decided after an initial PK study) to be given at intervals to be decided after PK data, is available for 72h. Oral liquid via nasogastric tube.
Intervention Type
Drug
Intervention Name(s)
Melatonin
Other Intervention Name(s)
N-acetyl-5-methoxytryptamine
Intervention Description
Oral liquid
Primary Outcome Measure Information:
Title
Completion of enrollment of 10 patients to Stage 1
Description
Stage 1= first 5 patients 50mg, second 5 patients 100mg oral melatonin liquid, open label
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Composite pharmacokinetic measures for each dose in Stage 1 (T max, CMax and AUC)
Description
T max, CMax and AUC of melatonin and 6-hydroxymelatonin sulphate levels at two doses of melatonin.
Time Frame
6 months
Title
Composite biomarker measures in Stage 2 ( linear discriminant analysis, hierarchical regression and hierarchical cluster analysis)
Description
Multiplex biomarker analysis will be used; linear discriminant analysis, hierarchical regression and hierarchical cluster analysis will be used to explore relationships between biomarkers
Time Frame
2 years
Title
28d all cause mortality in Stage 2
Description
Survival status at 28d
Time Frame
2 years
Title
Arterial blood lactate (stage 1 and stage 2)
Description
Absolute arterial lactate measures at various time points; change over time.
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Adult patients (16 years or over) on the ICU at Aberdeen Royal Infirmary with sepsis due to community acquired pneumonia who are within 24h of fulfilling the criteria for sepsis with clinical suspicion of pneumonia and the presence of chest X-ray changes consistent with pneumonia will be recruited. The criteria for sepsis are:
clinical suspicion or evidence of acute infection
systemic inflammatory response syndrome, defined by two or more of the following:
Core temperature <36 or >38°C;
tachycardia: heart rate > 90 beats/min;
tachypnoea: respiratory rate > 20 breaths/min or ventilated;
leucocyte count >12 x 109/L or <4 x 109/L.
Exclusion Criteria:
<16 years old,
have a life expectancy <24h,
have metastatic cancer or immunosuppression,
are receiving steroids (>20mg/d prednisolone or equivalent, used regularly for >2 weeks prior to ICU admission)
women of child bearing potential without a negative pregnancy test or a history of surgical sterilization.
patients receiving fluvoxamine or nifedipine,
have overt hepatic failure
unable to tolerate oral medication
known to be hypersensitive to trial medication and/or excipients
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Helen Galley
Organizational Affiliation
Univetsity of Aberdeen
Official's Role
Study Director
Facility Information:
Facility Name
Aberdeen Royal Infirmary
City
Aberdeen
State/Province
Scotland
ZIP/Postal Code
AB41 8TK
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
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Dose Assessment of Melatonin in Sepsis Trial
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