Condition category
Infections and Infestations
Date applied
01/07/2014
Date assigned
29/08/2014
Last edited
19/02/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Sepsis is a common condition caused by an infection, whereby the body’s immune system goes into “overdrive”. It can lead to, among other things, widespread inflammation, body swelling and a drop in blood pressure. Low blood pressure can then result in a reduced blood supply to vital organs, such as the brain and the heart. If not treated quickly, sepsis can cause multiple organ failure and death. Sepsis is a major cause of death for patients in intensive care units (ICU). Some 30% of patients currently die from the condition. Melatonin is a hormone naturally produced in the body. It is often referred to as the “sleep hormone” as it is given as a medicine to help people with insomnia (difficulty sleeping). However, it has proved to be a very versatile molecule; scientists has shown that it may have many health benefits. One of these is its antioxidant effects, mopping up the otherwise cell-damaging free radicals in our bodies. Research has also found that it reduces the inflammatory response to infection. We have recently undertaken a study that showed that, in healthy people, doses of oral melatonin are well tolerated and have no side effects. In this study, we want to find out two things. The first is whether or not oral melatonin is well tolerated in patients with sepsis as well as in healthy people. The second is whether the hormone is safe and how well it treats sepsis in patients compared to a placebo, or dummy, pill. The ultimate aim is to reduce the number of patients that die from sepsis, but for this early study, we hope to be able to identify a substance we can measure in blood which reflects the beneficial effect of melatonin.

Who can participate?
Patients over 16 years of age that have, or are suspected of having, sepsis and showing signs of pneumonia.

What does the study involve?
The study has two stages. In stage 1, two small groups of patients are given one dose of either 50mg or 100mg of melatonin. This is done to see whether the doses are well tolerated in sepsis patients. In stage 2, patients are randomly allocated into one of two groups. Patients in group 1 are given melatonin for 72 hours. Patients in group 2 are given a placebo. The effects of the hormone compared to the placebo are then analysed, using a number of measures.

What are the possible benefits and risks of participating?
For those patients given melatonin there is possibility of benefit by reduction of inflammation.

Where is the study run from?
The University of Aberdeen (UK)

When is the study starting and how long is it expected to run for?
October 2014 to June 2017

Who is funding the study?
Chief Scientist Office for Scotland. (UK)

Who is the main contact?
Professor Helen Galley
(see contact details below)

Trial website

Contact information

Type

Scientific

Primary contact

Prof Helen Galley

ORCID ID

http://orcid.org/0000-0002-9517-0074

Contact details

Institute of Medical Sciences
School of Medicine and Dentistry
College of Life Sciences and Medicine
University of Aberdeen
Aberdeen
AB25 2ZD
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

3/035/14

Study information

Scientific title

Dose Assessment of Melatonin in SEpsis triaL: a pilot phase I/II study

Acronym

DAMSEL 2

Study hypothesis

DAMSEL 2 is a pilot Phase I/II study in patients with sepsis. Stage 1 will assess the pharmacokinetics of melatonin and its major metabolite after 2 doses of exogenous melatonin 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.

Ethics approval

Scotland A REC, 16/12/2014, ref: 14/SS/1078

Study design

Stage 1: Phase I, open label, two-dose cohort study in patients with sepsis.
Stage 2: Phase II pilot double blinded randomised controlled trial of melatonin in patients with sepsis.

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Sepsis due to community acquired pneumonia

Intervention

Stage 1: Two small groups of patients will receive a single dose of either 50mg or 100mg of melatonin.
Stage 2: Patients will be randomly allocated into either:
Group 1 - these patients will receive melatonin for 72 hours
Group 2 - these patients will receive a placebo for 72 hours

Intervention type

Other

Phase

Phase I

Drug names

Primary outcome measures

Stage 1: Adminstration of 2 oral melatonin doses with no SUSARs
Stage 2: Approval by the DMC of dose and dosing interval decisions
The ultimate goal of experimental therapies in sepsis is reduced mortality. However, using mortality as an endpoint in a pilot study such as this is clearly not feasible. We will use a panel of biomarkers which are surrogates of outcome from sepsis.

All outcomes other than final outcome will be measured daily during the ICU stay. Final outcome is mortality at 28d.

Secondary outcome measures

1. Tissue specific injury markers, cytokines, adhesion molecules and chemokines: IL-1 beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-18, pentraxin-3, RANTES, MCP-1, MIP1alpha NGAL, SP-D, MMP-9, VCAM-1, P-selectin and TIMP-1.
2. Key clinical parameters including: heart rate, mean arterial pressure, temperature, acute physiologial and chronic health evaluation (APACHE) II score, length of ICU stay, ICU- and 28 day- all cause mortality, daily sequential organ failure score, time on vasopressor support
3. Time on the ventilator and ventilator settings such as positive end expiratory pressure, peak inspiratory pressure and minute volume
4. Ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FIO2 ratio)

All outcomes other than final outcome will be measured daily during the ICU stay. Final outcome is mortality at 28d.

Overall trial start date

01/10/2014

Overall trial end date

01/06/2017

Reason abandoned

Eligibility

Participant inclusion criteria

Patients who are within 24h of fulfilling the criteria for sepsis with clinical suspicion of community acquired 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 plus systemic inflammatory response syndrome, defined by two or more of the following:
1. Core temperature <36 or >38°C
2. Tachycardia: heart rate > 90 beats/min
3. Tachypnoea: respiratory rate > 20 breaths/min or ventilated
4. Leucocyte count >12 x 10^9/L or <4 x 10^9/L

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

10 + 40

Participant exclusion criteria

1. Anyone <16 years old
2. Life expectancy <24h
3. Metastatic cancer or immunosuppression
4. Taking steroids (>20mg/d prednisolone or equivalent, used regularly for >2 weeks prior to ICU admission)
5. Premenopausal females without a negative pregnancy test or a history of surgical sterilization.
6. Patients receiving fluvoxamine or nifedipine
7. Consent refusal

Recruitment start date

01/06/2016

Recruitment end date

31/05/2018

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Aberdeen Royal Infirmary
Intensive Care Unit
Aberdeen
AB25 2ZN
United Kingdom

Sponsor information

Organisation

University of Aberdeen/NHS Grampian (UK)

Sponsor details

Research Governance Office
Foresterhill House Annexe
Foresterhill
Aberdeen
AB25 2ZB
United Kingdom

Sponsor type

University/education

Website

Funders

Funder type

Government

Funder name

Chief Scientist Office for Scotland. ETM/358 (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

To be confirmed at a later date

Intention to publish date

Participant level data

Not expected to be available

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

On 19/02/2016 the overall trial end date was changed from 30/09/2016 to 01/06/2017.