SepsisPhase 1/2DAMSEL2NCT02319265
Dose Assessment of Melatonin in Sepsis Trial
A Phase 1/2 study testing Melatonin in people with Sepsis, run by University of Aberdeen at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Sepsis
- What is being tested?
- Melatonin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Apr 2017to Dec 2019
- Phase
- Phase 1/2
- 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 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- <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,
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- have overt hepatic failure
- unable to tolerate oral medication
- known to be hypersensitive to trial medication and/or excipients
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Aberdeen Royal Infirmary
Aberdeen, Scotland, AB41 8TK
About this study
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.
Read the 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.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MelatoninDrug
Also called N-acetyl-5-methoxytryptamine
Oral liquid
| Study group | Role | What they receive |
|---|---|---|
| Melatonin | Experimental | 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. Receives: Drug: Melatonin |
| Placebo | Placebo comparator | 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. Receives: Drug: Melatonin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Completion of enrollment of 10 patients to Stage 1
Stage 1= first 5 patients 50mg, second 5 patients 100mg oral melatonin liquid, open label
Measured: 6 months
Secondary outcomes (4)
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.
Measured: 6 months
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
Measured: 2 years
28d all cause mortality in Stage 2
Survival status at 28d
Measured: 2 years
Arterial blood lactate (stage 1 and stage 2)
Absolute arterial lactate measures at various time points; change over time.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Dec 2014 (estimated)
- Study startApr 2017 (estimated)
- Primary completionJun 2019 (estimated)
- Study completionDec 2019 (estimated)
Why it stopped: Study registered elsewhere and is not covered by FDA
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SepsisStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Aberdeen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Helen Galley, Study director, Univetsity of Aberdeen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02319265
- Sponsor's protocol ID
- 3/035/14
- Acronym
- DAMSEL2
- Status last verified
- Apr 2017
- First submitted
- 3 Dec 2014
- Last updated
- 21 Apr 2017
- Results posted
- No
- Data monitoring committee
- Yes
- 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 21 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dose Assessment of Melatonin in Sepsis Trial
- ClinicalTrials.gov ID
- NCT02319265
- Acronym / sponsor ID
- DAMSEL2 / 3/035/14
- Conditions
- Sepsis
- Keywords
- sepsis, antioxidant, melatonin, inflammation
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Study registered elsewhere and is not covered by FDA
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of AberdeenUniversity, hospital or other
- Study start
- Apr 2017 (estimated)
- Primary completion
- Jun 2019 (estimated)
- Study completion
- Dec 2019 (estimated)
- First posted
- 18 Dec 2014 (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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Melatonin | Experimental | Drug: MelatoninMelatonin 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 | Placebo comparator | Drug: MelatoninPlacebo 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. |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- 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:
Key exclusion criteria (9 listed)
- <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.
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: N-acetyl-5-methoxytryptamineOral liquid | Drug | Melatonin, Placebo |
Primary outcome
Completion of enrollment of 10 patients to Stage 1
Time frame: 6 months
Stage 1= first 5 patients 50mg, second 5 patients 100mg oral melatonin liquid, open label
4 secondary outcomes
Composite pharmacokinetic measures for each dose in Stage 1 (T max, CMax and AUC)
Time frame: 6 months
Composite biomarker measures in Stage 2 ( linear discriminant analysis, hierarchical regression and hierarchical cluster analysis)
Time frame: 2 years
28d all cause mortality in Stage 2
Time frame: 2 years
Arterial blood lactate (stage 1 and stage 2)
Time frame: 2 years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Apr 2017.
- 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.
Helen Galley study director
Univetsity of Aberdeen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Melatonin in people with Sepsis, run by University of Aberdeen at 1 site in United Kingdom.
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 7 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: withdrawn, as of the sponsor's last update on 21 Apr 2017. 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 United Kingdom. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 was withdrawn before enrolling participants, so there are no results.
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?
Completion of enrollment of 10 patients to Stage 1 (time frame: 6 months). 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 21 Apr 2017; AzTrials last refreshed its copy on 7 Nov 2026.