The Effect of Caffeine on the Narcoleptic Patients

Study Overview
=================
Brief Summary
-----------------
Caffeine may be playing a beneficial role in patients with narcolepsy. However, the relationship between caffeine and its effects on narcoleptic patients has not been examined, and it is also unclear whether caffeine provides a beneficial effect or not. Hence, the aim of this study is to assess the effects of caffeine consumption on daytime sleepiness and reaction time in narcoleptic patients.

Detailed Description
-----------------
The participants will be recruited at the University Sleep Disorders Center, College of Medicine, King Saud University. Narcolepsy diagnosis: Narcolepsy will be diagnosed based on the American Academy of Sleep Medicine International Classification of Sleep Disorders, 2014 (American academy of sleep medicine. International classification of sleep disorders (ICSD), 3rd ed. Darien, il: American academy of sleep medicine, 2014). The study will be interventional, randomized, double-blind, placebo control study, to evaluate the effect of caffeine on Narcoleptic Adults (n=30) aged 18-45 years old, following up in the Sleep Disorders Center (SDC) at King Khalid University Hospital (KKUH). Tools of the study: The study tools included an interview questionnaire, anthropometric measurements, indirect calorimetry, body composition measurements, blood biochemistry tests & Eye Blink measurement. Interview Questionnaire: For collecting data for this study, questionnaire well be designed. The questionnaire consisted of four parts to elicit the following information: A) Socio-demographic Data Personal data: The name of the participant, age, sex, educational level, and residence. Social habits: The smoking status Activity level: Mild, moderate or intense physical activity. B) Medical information: The occurrence of Narcolepsy with or without cataplexy. The occurrence of chronic diseases (hypertension, hyperlipidemia, cardiac diseases, diabetes and obesity). C) Caffeine expectancy & consumption, modified from: Caffeine expectancy questionnaire (CaffEQ) is a self-report measure, which assesses a range of expectancies for caffeine, and Sleep Disturbance (Huntley & Juliano, 2007). The Caffeine Consumption Questionnaire (CCQ) used to produce a typical week's average estimate of caffeine consumption in milligrams (Heaton, 2010). D) Daytime sleepiness Scales : Stanford Sleepiness Scale (SSS) The Karolinska Sleepiness Scale (KSS) Anthropometric measurements: The four selected anthropometric measures, see below: Weight Height for calculating body mass index (BMI) Waist circumference Hip circumference Indirect calorimetry An automated metabolic measuring cart used for determining Energy Expenditure and for providing key information about the nutrient mixture catabolized for energy by measuring the rates of O2 consumption (VO2) and CO2 production (VCO2), the device name is QUARK. Body Composition Measurement: The five variables selected for body composition measurements are: Fat mass Muscle mass Bone mass Total body water Visceral fat rating The body composition machine will be used is Bioelectrical impedance analysis (Tanita BC-418, Japan). Blood biochemistry tests: Fasting blood glucose, lipids Profile, CBC, LFT, CRP, Bone Profile, Vit D. Biochemical measurements will be done at KKUH, it is equipped with all needed matching to run this study and has well-trained technician and statics to help in performing the test needed. Eye Blink Measurement. Setting/Procedure In the day of study, subject need to come fasting overnight so their fasting blood glucose levels and lab test sample will be taken. Then the Anthropometric, Body Composition & Indirect calorimetry Measurement for the subject will be documented. The sample will be randomly divided using a software and the tablets will be identically packaged by the pharmacist in opaque capsules and administered orally in a double- blind setting to one of the following Groups: Group one: will receive 200 mg Caffeine capsule + water. Group two: will receive Placebo (fiber capsule) + water. Then instruct the patients to take the medication/placebo in the morning for 1 week and come back for reassessment: Random Blood sugar will be taken Blood Pressure will be measured. Eye Blink Measurement Daytime sleepiness Scales (part of the questioner data will be filled) We will have a baseline assessment, 1st assessment after single dose of 200 mg Caffeine or placebo and second assessment after one week of chronic use of medication in a dose 200 mg During the patient waiting time, the Interview Questionnaire will be filled. Data management: Data will be categorized to age, sex, social, anthropometric measurements, biochemistry lab test, psychological and medical status. Statistical analysis Data will be entered and statistically analyzed by SPSS software. ANOVA will be used to differentiate among treatment groups. In all the statistical comparisons, differences with p < 0.05 will be considered to be significant. Steps for assuring data quality include: Training: Educate data collectors in a structured manner. Data completeness: Using the hospital program (Cerner) that give immediate feedback on issues such as missing or out-of-range values & Excel software Data consistency: Compare across sites and over time. Data dictionary will be used e.g World Health Organization Drug Dictionary, Cerner program record for normal ranges. Ethical consideration The study was approved by KKUH Ethical committee, Saudi Food & Drug Authority & Saudi Clinical Trial Registry.

Official Title
-----------------
The Effect of Caffeine on the Narcoleptic Patients Randomized Controlled Clinical Trial

Conditions
-----------------
Narcolepsy

Intervention / Treatment
-----------------
* Drug: Vivarin
* Drug: Fiber


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Case -group should be Narcoleptic with cataplexy Exclusion Criteria: Individuals older than 45 years or younger than 18 years old. Individuals complaining of any diseases or conditions that affect their dietary intake, as such : renal failure, liver failure, malabsorption problems, cardiac diseases … etc. Individuals having hypersensitivity to caffeine. Individuals with medical conditions that cause sleepiness (like hypothyroidism) and pregnant or lactating females will be excluded.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Caffeine<br>Caffeine is an adenosine receptor antagonist. It inhibits a part of the sleep cycle and, in turn, promotes the wakefulness state. Generic name :Vivarin(1,3,7-trimethylxanthine), 200 mg/day for one week, Form of Administration:Oral in veg white capsule form (size 1) Drug Class:Central nervous system (CNS) stimulants. | Drug: Vivarin<br>* Adenosine is an endogenous sleep-promoting substance with neuronal inhibitory effects. Adenosine has been proposed to be a sleep-inducing substance accumulating in the brain during prolonged wakefulness. Caffeine is an adenosine receptor antagonist. It inhibits a part of the sleep cycle and, in turn, promotes the wakeup state. Caffeine results in the release of norepinephrine, dopamine and serotonin in the brain and the increase of circulating catecholamines, consistent with reversal of the inhibitory effect of adenosine.Vivarin Drug class :Central nervous system (CNS) stimulants.<br>* Other names: caffeine citrate;|
| Placebo Comparator: Fiber<br>Fiber powder will be used as placebo, Form of Administration:Oral in veg white capsule form (size 1) | Drug: Fiber<br>* Fiber will be used as placebo.<br>* Other names: Nutrisource Fiber;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Eye Blink Measurement | Blink total duration (BTD), which measures the duration of the closing, closed and reopening phases of each blink by using Optalert system, a glass frame carrying an IR transmitter and receiver bar that positioned below and in front of the eye, directed towards the lower edge of the upper eyelid allows for measurements of blink duration and eye closure time as an indicator of drowsiness and decreased vigilance.The eye blink measurement (Optalert) will be performed multiple times to measure the changes in the alertness level for each patient after single-dose intake and after daily medication intake.(The measuring instrument takes about 10-20 minutes). | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stanford Sleepiness Scale (SSS) | SSS is a daytime sleepiness Scales, using a 7-point Likert scale based on a series of statements that range from feeling active, vital, alert, wide awake to almost in reverie, cannot stay awake, sleep onset appears imminent describes how they feel at the time (Hoddes et.al,1973). | 7 days | 
| The Karolinska Sleepiness Scale (KSS) | KSS is a daytime sleepiness Scales, using a 9-point Likert scale based on a self-reported, subjective assessment of the subject's level of drowsiness at the time (Akerstedt & Gillberg, 1990). | 7 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Caffeine, Caffeine citrate, Neurological disorder, Excessive daytime sleepiness, Orexin, adenosine antagonist