Relationship of Nocturnal Concentrations of Melatonin, γ-aminobutyric Acid and Total Antioxidants With Insomnia

Relationship of Nocturnal Concentrations of Melatonin, γ-aminobutyric Acid and Total Antioxidants in Peripheral Blood With Insomnia After Stroke: Study Protocol for a Prospective Single-center Randomized Controlled Clinical Trial

To analyze the relationship of nocturnal concentrations of melatonin, γ-aminobutyric acid and total antioxidants with insomnia after stroke.

Study Overview

• Status: Unknown
• Conditions: Insomnia
• Intervention / Treatment: Other: insomnia group; Other: non-insomnia group; Other: normal control

Detailed Description

Sleep disturbance, especially insomnia, is a common complication after ischemic stroke for the patients during rehabilitation of cerebral infarction. Actually, more than half of ischemic stroke patients have insomnia complaints. Meanwhile, poor quality of sleep may greatly impede stroke rehabilitation and induce other complications. Thus, it is of importance to study the insomnia for the post-stroke patients, especially when they are during rehabilitation of cerebral infarction.

Melatonin is a pineal hormone with the peak nocturnal secretion. Melatonin typically takes a large responsibility in coordination with the circadian rhythms and further serves as a regulator in the sleep function. The secretion peak of melatonin is around midnight to 3:00 a.m.. Along with other antioxidants, the melatonin can also work as an effective neuroprotective enzyme against neurodegeneration and ischemic brain injury. Thus, the melatonin is known to take an important role in acute ischemic stroke, with a rhythm impairment and nocturnal decrease. γ-Aminobutyricacid (GABA) is likewise a strong sleep regulator that may activate GABA receptors as well as inhibitors of waking processes. It is known that GABA level in the human body is strongly associated with the impairment of patients in the acute ischemic stroke. Antioxidant may take a critical role in the balance of oxidation by scavenging free radicals, so it is regarded as an important marker in studying the insomnia for the post-stroke patients. However, to our knowledge, there is almost no report on simultaneous measurements of levels of melatonin, GABA and antioxidants in the bloods of patients during the convalescence of ischemic stroke or on studying their association with the insomnia complication for the post-stroke patients.

Therefore, this prospective single-center randomized controlled clinical trial was designed to investigate the relationship of nocturnal concentrations of melatonin, γ-aminobutyric acid and total antioxidants with insomnia after stroke by comparing the nocturnal concentrations of melatonin, GABA and total antioxidants in stroke patients with insomnia or without insomnia and normal controls.

Data management Clinical researchers accurately, completely, timely filled out the clinical trial observation form. Data were recorded electronically by data managers using a double-data entry strategy. The electronic database was locked by the project manager after checking. All data were analyzed statistically by professional statisticians. Anonymized trial data will be published at www.figshare.com.

Statistical analysis Data were presented as the mean ± standard deviation for normally distributed variables, or median values (P25, P75) for non-normally distributed variables. Student's t-tests or nonparametric Mann-Whitney tests were performed to compare the differences between normally distributed variables or non-normally distributed variables. For the analysis of biochemical test results, data were transferred to normal distribution and Hotelling's T2 tests were performed. Before entering variables into the regression model, centering predictor variables were performed to avoid nonessential collinearity. Binary logistic regression analysis was conducted to identify the association between variables or variables interaction and insomnia diagnosis after infarction. Multiple linear regression analysis was carried out to determine the correlation between variables or variables interaction and sleep-related scores, such as Epworth Sleepiness Scale scores, Pittsburgh Sleep Quality Index scores, Insomnia Severity Index scores, Morningness-Eveningness Questionnaire (Chinese version) scores and Fatigue Severity Scale scores by using backward method. P values < 0.05 were considered statistically significant. SPSS 22.0 software was used for statistical analysis.

• Study Type: Observational
• Enrollment (Actual): 75

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

This is a prospective single-center randomized controlled clinical trial in the China Rehabilitation Research Center. Stroke patients during rehabilitation have been recruited since July in 2014. After screening according to inclusion and exlcusion criteria, patients were assigned to insomnia group and non-insomnia group. Simultaneously, persons without stroke or insomnia served as normal controls. Each group contained 25 cases.

Description

Inclusion Criteria:

• Infarction occurred in the middle cerebral artery blood supply area (Identified by medical record, magnetic resonance imaging, magnetic resonance angiography, computed tomography or computed tomography angiogram)
• Diagnostic criteria for insomnia of Diagnostic and Statistical Manual of Mental Disorders (4th edition)
• Course of disease ≥ 3 months
• Mini-Mental State Examination > 27
• Age ranged from 50 to 70 years old
• Right handedness

Exclusion Criteria:

• Cognitive and language disorders
• History of rheumatism, cancer, severe liver and kidney dysfunction, benign prostatic hyperplasia, and severe cardiac insufficiency, besides hypertension, diabetes, and coronary atherosclerotic heart disease
• High-risk sleep apnea, i.e., STOP-Bang Questionnaire ≥ 3
• Unexplained limb pain, many times of getting up in the night to urinate or restless legs syndrome
• Frequency of application of sleeping drugs > once/week or the use of psychotropic drugs, such as anti-anxiety and depression drugs, and antipsychotic drugs
• Frequency of drinking coffee and other stimulating drinks > three times/week
• Drug or alcohol abuse
• Insomnia caused by poor sleeping conditions, such as noise, light, and bedmate interference
• Insomnia before affecting stroke
• Hamilton Depression Scale > 20 or Hamilton Anxiety Scale > 14
• Participation in other clinical trials

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
insomnia group; After screening according to inclusion and exclusion criteria, patients were assigned to insomnia group that contained 25 cases.	Other: insomnia group; After screening according to inclusion and exclusion criteria, patients were assigned to insomnia group that contained 25 cases.
non-insomnia group; After screening according to inclusion and exclusion criteria, patients were assigned to non-insomnia group that contained 25 cases.	Other: non-insomnia group; After screening according to inclusion and exclusion criteria, patients were assigned to non-insomnia group that contained 25 cases.
normal control; persons without stroke or insomnia served as normal controls that contained 25 cases.	Other: normal control; Persons without stroke or insomnia served as normal controls that contained 25 cases.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nocturnal concentrations of melatonin	Melatonin is a pineal hormone with the peak nocturnal secretion. Melatonin typically takes a large responsibility in coordination with the circadian rhythms and further serves as a regulator in the sleep function. The secretion peak of melatonin is around midnight to 3:00 a.m.. Along with other antioxidants, the melatonin can also work as an effective neuroprotective enzyme against neurodegeneration and ischemic brain injury. Thus, the melatonin is known to take an important role in acute ischemic stroke, with a rhythm impairment and nocturnal decrease.	1 day at 3:00 a.m

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
National Institute of Health Stroke Scale	A tool used for quantifying stroke severity. The full score is 42. High score suggests severe nerve injury.	1 day at 3:00 a.m

Collaborators and Investigators

• Sponsor: China Rehabilitation Research Center
• Investigators: Principal Investigator: Wei Zhang, Ph.D, China Rehabilitation Research Center

Publications and helpful links

General Publications

• Zhang W, Li F, Zhang T. Relationship of nocturnal concentrations of melatonin, gamma-aminobutyric acid and total antioxidants in peripheral blood with insomnia after stroke: study protocol for a prospective non-randomized controlled trial. Neural Regen Res. 2017 Aug;12(8):1299-1307. doi: 10.4103/1673-5374.213550.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2011
• Primary Completion (Anticipated): December 1, 2018
• Study Completion (Anticipated): March 1, 2019

Study Registration Dates

• First Submitted: June 27, 2017
• First Submitted That Met QC Criteria: June 27, 2017
• First Posted (Actual): June 28, 2017

Study Record Updates

• Last Update Posted (Actual): July 18, 2018
• Last Update Submitted That Met QC Criteria: July 16, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Sleep Initiation and Maintenance Disorders
• Other Study ID Numbers: ChinaRRC_01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No