Clinical trial NCT04057313: Coffee in Hemodialysis and Headache
Official title: Coffee Intake in HemoDialysis and Headache (CoffeeHD): a Randomized Double Blind Multicenter Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hemodialysis Complication
Keywords: Coffee
Headache
Intra-dialytic hypotension
Lead sponsor: Saint-Joseph University
Sponsor class: OTHER
First posted: 2019-08-15
Enrollment: 156
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: Inclusion Criteria:

* All adult patients \> 18 years old on chronic hemodialysis

Exclusion Criteria:

* patients with a history of chronic or paroxysmal atrial fibrillation
* patients on chronic systematic pain killers
* patients with a problem of swallowing food or drinks
* patients who are coffee allergic or intolerant.

Primary outcomes:
measure: number of headache episodes
timeFrame: 4 weeks
Secondary outcomes:
measure: number of intra-dialytic hypotensive episodes
timeFrame: 4 weeks
measure: number of sleeping hours per night
timeFrame: 4 weeks
measure: energy after dialysis
timeFrame: 4 weeks
measure: irritability
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Ajaltoun
country: Lebanon
facility: Saint-Georges Hospital
state: Kesrouan
Study officials:
affiliation: Saint-Joseph University
name: Mabel Aoun, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Aoun MH, Hilal N, Beaini C, Sleilaty G, Hajal J, Boueri C, Chelala D. Effects of Caffeinated and Decaffeinated Coffee on Hemodialysis-Related Headache (CoffeeHD): A Randomized Multicenter Clinical Trial. J Ren Nutr. 2021 Nov;31(6):648-660. doi: 10.1053/j.jrn.2021.01.025. Epub 2021 Mar 12.