Coffee in Hemodialysis and Headache
Condition: Hemodialysis Complication
MeSH terms: Headache
Study type: Interventional

Summary: 
      Coffee is the most consumed drink worldwide, sometimes needed to boost energy and other times
      to entertain social connectivity. Caffeine is mostly present unbound in the plasma, only 10
      to 30% of caffeine binds to plasma proteins. It is distributed freely into the intracellular
      space, and it has a small distribution volume. Therefore, caffeine can pass through the
      dialysis membrane during a standard hemodialysis session. In hemodialysis patients, headache
      occurs in 40 to 75% of patients. Some authors have suggested that one of the reasons of
      headache during hemodialysis is caffeine withdrawal. This trial aims to find whether coffee
      intake during hemodialysis reduces the headache episodes. It is a randomized double blind
      multicenter trial where 160 patients will be randomized to 2 groups: group 1 of 80 patients
      will be given a cup of coffee each dialysis session for 4 weeks and group 2 will receive
      decaffeinated coffee each dialysis session for 4 weeks.
    

Detailed description: 
      Coffee is the most consumed drink worldwide, sometimes needed to boost energy and other times
      to entertain social connectivity. It is known also to cause addiction and thus be a cause for
      withdrawal symptoms such as headache and irritability. Coffee is not contra-indicated in
      patients with chronic kidney disease. Caffeine is mostly present unbound in the plasma, only
      10 to 30% of caffeine binds to plasma proteins. It is distributed freely into the
      intracellular space, and it has a small distribution volume within the body around 0,7L/kg.
      Therefore, caffeine can pass through the dialysis membrane during a standard hemodialysis
      session. In hemodialysis patients, intra-dialytic hypotension, fatigue post-dialysis and
      headache occur in 40 to 75% of patients. Some authors have suggested that one of the reasons
      of headache during hemodialysis is caffeine withdrawal.

      This trial aims to find out whether coffee consumption during dialysis could decrease
      headache episodes.

      Methods

      Study setting All patients on chronic hemodialysis in three Lebanese dialysis units,
      Saint-Georges Ajaltoun hospital, Hôtel-Dieu de France and Bellevue Medical Center will be
      included.

      Trial design and participants This is a randomized, controlled, double-blind, multi-center
      clinical trial. Patients will be randomized to one of two arms and then group one will
      receive the coffee during hemodialysis session and group two will receive decaffeinated
      coffee.

      Blinding will be ensured by designating an external employee that will hold the cups of
      coffee to the unit's nurses every day with the name of each patient on the cup.

      Randomization Patients will be assigned to receive coffee during hemodialysis or not using a
      1:1 allocation ratio.

      Interventions Patients will be randomly assigned to one of two groups: Group 1 will receive a
      cup of coffee (80 cc) in the middle of the dialysis session every session for 4 weeks. Group
      2 will receive non-caffeinated cup of coffee (80 cc) in the middle of the dialysis session
      every session for 4 weeks. The coffee that will be used is the boiled unfiltered Arabica
      coffee with a ratio of water to coffee of 800 ml/125 g. Patients can add sugar to their
      coffee if they want. Ultrafiltration rate will not exceed 13 mL//kg/hour for all included
      patients.

      Participant timeline Every patient will be followed from first day of randomization till the
      end of the month (4 weeks follow-up).

      Sample size calculation If we consider a two-sided alpha of 5% and power of 90% and a
      prevalence of headache in the dialysis population up to 75% that will be reduced by 25% in
      the group taking caffeine, the total sample size needed would be 160 patients, 80 in each
      arm.

      Data collection

      Variables that will be collected include:

        -  Personal information: age, sex, smoking, alcohol intake per week, hypertension (at least
           one antihypertensive drug)

        -  Caffeine intake: number of coffee cups at home per day (outside the dialysis session),
           coffee intake before the dialysis session (yes/no), coffee intake during the dialysis
           session (yes/no)

        -  Medical history: diabetes, hypertension, coronary artery disease, history of headache or
           migraine

        -  Medications: beta blockers, antidepressants, benzodiazepine

        -  Dialysis sessions related information: dialysis vintage (months), urea reduction ratio
           (URR) of the month

        -  Clinical variables: number of intra-dialytic hypotensive the month before the trial and
           during the trial, number of intra-dialytic and home headache episodes during the trial,
           pre-dialysis systolic and diastolic blood pressure and heart rate of the first and the
           last session of the trial, insomnia before and at the end of the trial, energy after a
           dialysis session before and after the trial and irritability before and after the trial.

        -  Adverse events will be also reported such as arrhythmia, tachycardia or hypertension.

      Statistical analysis Continuous variables will be presented as mean ± standard deviation (SD)
      and categorical variables as percentages. The effectiveness of the randomization will be
      checked by comparing baseline variables with the appropriate tests.

      The analysis will depend on the distribution of the outcome variables:

      If outcome variables are normally or quasi-normally distributed, Hotelling's T-Squared will
      be used as an overall multivariate test for the difference between the 2 groups, followed by
      t-tests to assess individual outcomes.

      If outcome variables are skewed, the Mann-Whitney test will be used. Bonferroni correction
      will be used to adjust for multiple comparisons. A P-value of ≤0.05 is considered
      statistically significant.

      Definitions Hypotensive episodes are defined as drop of systolic blood pressure below 90 mmHg
      or of 20 mmHg accompanied with clinical symptoms such as muscle cramps, chest pain, dyspnea,
      dizziness, headache, abdominal pain, nausea, vomiting, weakness, anxiety, paleness and
      sweating. Hypotensive episodes during dialysis usually occur in 15-30% of cases.

      Irritability and energy will be assessed based on two questions:

        -  Have you been a very nervous person, irritated by minor incidents? (yes/no)

        -  How much energy do you feel after your dialysis session on a scale from 1 to 10?

      Insomnia will be assessed by two questions: have you any difficulty sleeping at night?
      (yes/no), how many hours do you sleep at night?

      Ethical approval The study will get approval from the ethics committee of Saint-Joseph
      University and is in agreement with the Helsinki Declaration of 1975.
    

Intervention name(s): Coffee
Intervention type(s): Dietary Supplement
Intervention description(s): Coffee used will be the boiled unfiltered Arabica coffee
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: A randomized multicenter trial: hemodialysis patients in three dialysis units will be randomized to two groups, group 1 will take coffee for 4 weeks, group 2 will take decaffeinated coffee for 4 weeks
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Coffee; Headache; Intra-dialytic hypotension