Dose Assessment of Melatonin in Sepsis Trial

Sepsis Clinical Trial

— DAMSEL2  

Official title:

Dose Assessment of Melatonin in Sepsis Trial

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02319265
• Other study ID #: 3/035/14
• Status: Withdrawn
• Phase: Phase 1/Phase 2
• First received: December 3, 2014
• Last updated: April 20, 2017
• Start date: April 2017
• Est. completion date: December 2019

Study information

• Verified date: April 2017
• Source: University of Aberdeen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 2019
• Est. primary completion date: June 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

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:

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 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

Related Conditions & MeSH terms

• Sepsis
• Toxemia

Intervention

Drug:
• Melatonin
Oral liquid

Locations

Country	Name	City	State
United Kingdom	Aberdeen Royal Infirmary	Aberdeen	Scotland

Sponsors (1)

Lead Sponsor	Collaborator
University of Aberdeen

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Completion of enrollment of 10 patients to Stage 1	Stage 1= first 5 patients 50mg, second 5 patients 100mg oral melatonin liquid, open label	6 months
Secondary	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.	6 months
Secondary	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	2 years
Secondary	28d all cause mortality in Stage 2	Survival status at 28d	2 years
Secondary	Arterial blood lactate (stage 1 and stage 2)	Absolute arterial lactate measures at various time points; change over time.	2 years