Exploratory Study of Melatonin Induced Sleep Regularization in Severe Brain Injury

NCT02732288 | Terminated

• 1 other identifier: NSC-0894
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with severe brain injuries often have slow accumulating recoveries of function. In ongoing studies, we have discovered that elements of electrical activity during sleep may correlate with the level of behavioral recovery observed in patients. It is unknown whether such changes are causally linked to behavioral recovery. Sleep processes are, however, associated with several critical processes supporting the cellular integrity of neurons and neuronal mechanisms associated with learning and synaptic modifications. These known associations suggest the possibility that targeting the normalization of brain electrical activity during sleep may aid the recovery process. A well-studied mechanism organizing the pattern of electrical activity that characterizes sleep is the body's release of the substance melatonin. Melatonin is produced in the brain and released at a precise time during the day (normally around 8-10PM) to signal the brain to initiate aspects of the sleep process each day. Ongoing research by other scientists has demonstrated that providing a small dose of melatonin can improve the regular pattern of sleep and help aid sleep induction. Melatonin use has been shown to be effective in the treatment of time change effects on sleep ("jet lag") and mood disturbances associated with changes in daily light cues such as seasonal affective disorder. We propose to study the effects of melatonin administration in patients with severe structural brain injuries and disorders of consciousness. We will measure the patient's own timing of release of melatonin and provide a dose of melatonin at night to test the effects on the electrical activity of sleep over a three month period. In addition to brain electrical activity we will record sleep behavioral data and physical activity using activity monitors worn by the patients. Patient subjects in this study will be studied twice during the three month period in three day inpatient visits where they will undergo video monitoring and sampling of brain electrical activity using pasted electrodes ("EEG"), hourly saliva sampling for one day, and participation in behavioral testing.

Conditions

Disorders of Consciousness

Outcome Measures

Primary Outcomes (1)

• Changes in in sleep/wake architecture following melatonin administration as assessed by time domain analysis of sleep EEG

  baseline, 3 months

Secondary Outcomes (3)

• quantitative measures of EEG spectral content

  baseline, 3 months

• Changes in wakeful behavior level

  baseline, 3 months

• Activity levels captured by Actigraph device

  baseline, 3 months

Study Arms (2)

Melatonin, brain injured patients

EXPERIMENTAL

Melatonin 3mg, orally, at 8pm, daily for 3 months

Dietary Supplement: melatonin

Healthy volunteers

EXPERIMENTAL

Melatonin 3mg, orally, at 8pm

Dietary Supplement: melatonin

Interventions

melatonin DIETARY_SUPPLEMENT

After measuring the subject's own timing of release of melatonin, subjects will be provided a dose of melatonin at 8pm to test the effects on the electrical activity of sleep, measured using electroencephalography. The same intervention will be given to healthy, non-brain injured controls.

Healthy volunteers; Melatonin, brain injured patients

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject's legally authorized representative must be fluent in English
• Subject must have been able to speak English prior to the brain injury occurrence
• Subject must have previously participated in the NSC-0764 study at Rockefeller University Hospital or New York Presbyterian-Cornell
• Subject must be diagnosed with a severe nonprogressive brain injury
• Subject must be medically stable
• Subject must be between 18 and 65 years of age
• Male and female subjects accepted
• Subject must have previously participated in studies with EEG data that identify elements of sleep architecture (evidence of components of at least 1 of the following: Stage 2 features (e.g. spindles K complexes, or vertex waves) or stage 3 features (e.g. slow waves), including the NSC-0764 study, and this data must be available to the PI.
• HEALTHY VOLUNTEERS: case matched to the study population +/- 5 years; fluent in English; ability to sit still for several consecutive hours; must sleep normal hours consistently (approximately 10 pm - about 6 am) and not be a shift worker

You may not qualify if:

• Refractory generalized seizures
• Ventilator dependency
• Evidence of Alzheimer's Disease or dementia preinjury
• Currently taking melatonin
• Dialysis dependency
• Premorbid neuropsychiatric history (Axis I requiring prior hospitalization)
• History of severe asthma (requiring hospitalization)
• Participation in any investigational trial within 30 days prior to enrollment in this study
• History of any sleep disorder or restless leg syndrome pre-injury
• Medical history, physical examination, or laboratory findings suggestive of any other medical or psychological condition that would, in the opinion of the principal investigator, make the candidate ineligible for the study
• HEALTHY VOLUNTEERS: current or past medical history of any neurological disease or cardiovascular disease, sleep disorder, teeth grinding or restless leg syndrome (RLS); taking any medications with any neurologic effects, any medical condition that disrupts sleep; participation in NSC-0764; Body Mass Index (BMI) \> 30 kg/m2;

Sponsors & Collaborators

• Rockefeller University: lead
• Weill Medical College of Cornell University: collaborator

Study Sites (1)

The Rockefeller University

New York, New York, 10065, United States

Location

Related Publications (14)

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MeSH Terms

Conditions

Consciousness Disorders

Interventions

Melatonin

Condition Hierarchy (Ancestors)

Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

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

Study Officials

• Nicholas Schiff, MD

  Weill Cornell Medical College/ Rockefeller University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 4, 2016
• First Posted: April 8, 2016
• Study Start: May 1, 2016
• Primary Completion: June 19, 2018
• Study Completion: June 19, 2018
• Last Updated: May 30, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)