Dose Assessment of Melatonin in Sepsis Trial

NCT02319265 | Withdrawn Phase 1 DMC

• 1 other identifier: 3/035/14
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Sepsis

Keywords

sepsis; antioxidant; melatonin; inflammation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Composite pharmacokinetic measures for each dose in Stage 1 (T max, CMax and AUC)

  6 months

• Composite biomarker measures in Stage 2 ( linear discriminant analysis, hierarchical regression and hierarchical cluster analysis)

  2 years

• 28d all cause mortality in Stage 2

  2 years

• Arterial blood lactate (stage 1 and stage 2)

  2 years

Study Arms (2)

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.

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.

Drug: Melatonin

Interventions

Melatonin DRUG

Oral liquid

Also known as: N-acetyl-5-methoxytryptamine

Melatonin; Placebo

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• \<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

Sponsors & Collaborators

• University of Aberdeen: lead

Study Sites (1)

Aberdeen Royal Infirmary

Aberdeen, Scotland, AB41 8TK, United Kingdom

Location

MeSH Terms

Conditions

Sepsis; Inflammation

Interventions

Melatonin

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Tryptamines; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Helen Galley

  Univetsity of Aberdeen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2014
• First Posted: December 18, 2014
• Study Start: April 1, 2017
• Primary Completion: June 1, 2019
• Study Completion: December 1, 2019
• Last Updated: April 21, 2017

Record last verified: 2017-04

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)