Impact of Head of Bed Elevation in Symptoms of Patients With Gastroesophageal Reflux Disease: a Randomized Single-blind Study
Phase: NA
Conditions: Gastroesophageal Reflux Disease
Sponsor: Universidad Nacional de Colombia

 
 
IMPACT OF HEAD OF BED 
ELEVATION IN SYMPTOMS OF 
PATIENTS WITH 
GASTROESOPHAGEAL REFLUX 
DISEASE: A RANDOMIZED 
SINGLE-BLIND STUDY 
(IBELGA) 
 
INTERNAL MEDICINE POSTGRADUATE 
THESIS PROTOCOL 
 
 
 
M E N T O R :  W I L L I A M  O T E R O  R E G I N O  
R E S I D E N T :  I V Á N  M A U R I C I O  V I L L A M I L  M O R A L E S  
R E S I D E N T :  D A N I E L  M A U R I C I O  G A L L E G O  O S P I N A  
 
 
 
 
B O G O T Á  D . C .  
M A R C H  2 N D ,  2 0 1 7  

EXECUTIVE SUMMARY 
 
Background: Gastroesophageal reflux disease is a very frequent clinical condition and nocturnal 
symptoms are a cause of quality of life impairment, poor sleep quality and absenteeism. Because of 
factors such as a prolonged acid exposure during sleep, nocturnal reflux has been associated to 
esophagitis, more extra-esophageal symptoms and other illnesses such as asthma. Head of bed 
elevation, as a low-cost non pharmacologic anti-reflux treatment is nowadays recommended, but its 
clinical impact in patients with nocturnal symptoms remains unknown due to inconsistent results and 
methodological limitations among different clinical trials, most of which were performed before the 
widespread use of proton pump inhibitors in clinical practice.  
Hypothesis: Head of bed elevation is a useful treatment for patients with gastroesophageal reflux 
disease and nocturnal symptoms, and has a positive impact in quality of life in these patients. 
Study Objective: To assess the effectiveness of head of bed elevation for treatment of patients with 
gastroesophageal reflux disease and nocturnal symptoms, and to determine the impact of this 
intervention in quality of life of these patients. 
Methods: Randomized single-blind single-centre controlled clinical trial with a 2x2 cross-over design. 
A sample of 42 patients attending to the outpatient gastroenterology unit at Clínica Fundadores in 
Bogotá city, who meet the inclusion criteria and have no exclusion criteria will be selected to 
participate. Included patients will be randomized to raise the head of bed with standard 20 cm-height 
wooden blocks or to sleep without bed inclination during the first 6 week period. After a 2 week 
washout period, allocation will be crossed and participants will be followed again during a second 6 
week period. During the trial, every patient will receive standard pharmacological treatment with a 
proton pump inhibitor and/or sodium alginate and the researchers in charge of statistical analysis and 
reporting results will be blinded for the non pharmacological intervention under study. Primary 
outcome is a significant symptom reduction according to RDQ validated questionnaire and secondary 
outcomes include quality of life impact according to SF-36 validated questionnaire, patient preference 
and adverse events of non pharmacological intervention. Statistical analysis will be carried out with 
STATA 13.0 (Special Edition) statistical package for Windows. Differences with a p<0,05 will be 
accepted as statistically significant. 
Expected results: Effectiveness of head of bed elevation in the treatment of patients with 
symptomatic nocturnal gastroesophageal reflux disease will be assessed. New knowledge for generation 
of a local and international recommendation about non pharmacological treatment of gastroesophageal 
reflux disease will be provided. Colombian researchers will be trained in methodological aspects 
concerning design, conduction and analysis of clinical trials in this field of medical knowledge. 
Keywords: Gastroesophageal reflux disease, head of bed elevation, lifestyle measures, nocturnal 
symptoms, quality of life. 
 
 
PROBLEM STATEMENT 
Gastroesophageal reflux disease (GERD) is a clinical condition characterized by troublesome 
symptoms and medical complications as a result of reflux of gastric contents into the esophagus1. 
GERD is diagnosed in 4% of primary care outpatient visits2 and the disease prevalence in Latin-
America reaches 12-31%3. Nocturnal symptoms have been found in 74% of patients with GERD and 
are a cause of significant quality of life impairment, when compared with general population and 

patients with GERD and daytime-only symptoms4. Sleep interference secondary to nocturnal 
retrosternal burning has been associated to lower work productivity5, even in patients being treated 
with proton pump inhibitors (PPI)6. Due to several physiological factors such as lack of conscious 
perception of symptoms, reduced salivation and a lower frequency of nocturnal swallowing7, a 
significantly longer acid exposure overnight has been associated to the emergence of complications like 
esophagitis8, 9, more extra-esophageal symptoms10 and other illnesses such as asthma11. 
As a low-cost non pharmacological anti-reflux treatment for GERD, head of bed elevation (HBE) is 
nowadays moderate-strength recommendation with a low level of evidence12-15. Clinical impact of this 
measure in patients with night-time symptoms remains unknown, due to inconsistent results and 
methodological limitations among different clinical trials; most of which were performed before the 
widespread use of proton pump inhibitors in clinical practice. Evidence from several non-randomized 
studies suggest that HBE could reduce esophageal acid exposure time and could decrease GERD 
symptoms16-18; however, another study found no significant differences in those same outcomes19. On 
the other hand, all randomized controlled clinical trials published this far show inconsistent results. A 
study published before widely accepted clinical use of PPI, revealed significant clinical and endoscopic 
improvement in patients with GERD and grade C-D esophagitis allocated to receive HBE, when 
compared with controls20. In contrast, a multi-centre clinical trial found no difference in symptom 
score or antacid use among groups allocated to HBE and control group21. All cited studies have 
methodological limitations and heterogeneity in outcome assessments, which makes difficult 
conducting a meta-analysis with these data22, 23. No published studies evaluating impact of HBE in 
quality of life or work productivity were found. Table 1 summarizes published evidence to date. 
 
 
Study [Population] 
Jadad 
score 
Follow-up 
n 
Major findings 
Main limitation 
Reference 
Stanciu C, 1977 
[GERD]  
1 
15 hours 
63 
↓ acid exposure time, 
clinical improvement 
Non-randomized 
Short follow-up  
16 
Johnson L, 1981 
[GERD]  
0 
ND 
55 
↓ acid exposure time 
Non-randomized 
No symptom assessment  
17 
Harvey R, 1987  
[C/D Esophagitis] 
3 
6 weeks 
71 
Clinical and endoscopic 
improvement 
Pre-PPI era 
20 
Hamilton J, 1988 
[Esophagitis] 
3 
3 days 
15 
No acid exposure time 
reduction nor clinical 
improvement 
 
Low power 
Short follow-up  
19 
Pollmann H, 1996 
[GERD]  
NA 
2 weeks 
NA 
No clinical improvement 
Full text unavailable 
Non-structured abstract 
21 
Khan BA, 2012 
[Nocturnal GERD]  
1 
1 week 
20 
↓ acid exposure time, 
clinical improvement 
Non-randomized  
Inpatient setting  
18 
Table 1: Summary of HBE clinical trials in GERD published to date. NA: Unavailable; PPI: proton 
pump inhibitor; ↓: reduction 
 
 
 

HYPOTHESIS 
Head of bed elevation is a useful treatment for patients with GERD and nocturnal symptoms, and has 
a positive impact in quality of life in these patients. 
 
 
STUDY OBJECTIVES 
General Objective: To assess the effectiveness of HBE for treatment of patients with GERD and 
nocturnal symptoms, and to determine the impact of this intervention in quality of life of these 
patients. 
Specific Objectives: 
1. To identify, recruit and randomize participants with strict allocation concealment. 
2. To compare symptom severity and quality of life among participants allocated to the HBE 
and the control group, in both the first and second period of study. 
3. To assess therapeutic adherence and adverse event occurrence periodically by means of 
telephone call and photographic documentation of patient compliance with assigned 
intervention. 
 
PATIENTS AND METHODS 
General design: Randomized single-blind single-centre controlled clinical trial with a 2x2 cross-over 
design, in a sample of patients attending to the outpatient visit at the Gastroenterology, Digestive 
endoscopy and Liver Diseases Unit in Clínica Fundadores, Bogotá city. Participants who meet the 
inclusion and have no exclusion criteria will be randomized to raise the head of bed with standard 20 
cm-height wooden blocks or to sleep without bed inclination during 2 periods of 6 weeks each, 
separated by a washout 2 week period. During the trial, every patient will receive standard 
pharmacological treatment with a proton pump inhibitor and/or sodium alginate, according to treating 
physician criteria, and the researchers in charge of statistical analysis and reporting results will be 
blinded for the non pharmacological intervention under study. Primary outcome is a significant 
symptom reduction according to RDQ validated questionnaire and secondary outcomes include quality 
of life impact according to SF-36 validated questionnaire, patient preference and adverse events of non 
pharmacological intervention. 
The trial will be conducted during 8 months and will be divided into 4 successive stages.  
1. Stage I: 2 months during which the first 4 specific objectives will be accomplished. 
2. Stage II: 4 months for specific objectives 5 to 7. 
3. Stage III: 1 month for specific objective 8 and results discussion. 
4. Stage IV: 1 month for specific objectives 9 and 10. 

In figure 1 and table 2, different stages with respective component activities are outlined. 
 
Figure 1: Clinical trial stages 
 
 
Patient recruitment: Because of a low recruitment rate, an active participant search system was finally 
implemented. This system was based on telephone calls, using a database with patient data from all 
upper gastrointestinal endoscopies performed in the Gastroenterology Unit at Clínica Fundadores in 
Bogotá city, between years 2014 to 2016. Patients were pre-selected based on endoscopically diagnosed 
erosive esophagitis of any grade, which is one of the clinical trial inclusion criteria. In order to minimize 
selection bias, 2 interviewers performed telephone calls in a consecutive chronologic order to all 
patients in the database without exception. In all cases, the same standardized telephone call format was 
used. 
 
Sample size: Null hypothesis (H0) and unidirectional alternative hypothesis (H1) of the trial are 
represented below: 
 
H0: RDQHBE= RDQNoHBE 
 
 
 
H1: RDQHBE<RDQNoHBE 
H0: SF-36HBE= SF-36NoHBE 
 
 
 
H1: SF-36HBE> SF-36NoHBE 
 
Sample size was estimated based on the hypothesis that HBE would produce a difference of at least 
10% in RDQ and SF-36 scores. Effect size (Cohen d) was calculated as 0,49 keeping in mind an RDQ 
mean and standard deviation of 3,3±1,0 previously found in Spanish population with symptomatic 
GERD24 and an SF-36 mean and standard deviation of 56,9±20,3 reported in Italian population in 
medical therapy with PPI25. The minimally important difference selection was chosen based on the 
assumption that any difference smaller than 10% would have no clinical relevance. Based on this data, 
14 patients per group would yield a power greater than 80% for detection of a minimally important 
difference as large as or larger than 0,6 points in RDQ questionnaire (range: 1 to 6) and 10 points in 
SF-36 questionnaire (range: 0 to 100), when using a paired t test as described in the statistical analyses 
plan section. Because of a complementary analysis of crossover data is planned with McNemar 
marginal homogeneity test, effect size was recalculated based on results of a previous trial20, according 
to which, 58,8 % and 28,6% of placebo-treated patients in pre-omeprazole era, reported improvement 
of GERD symptoms with and without a HBE of 20 cm, respectively. Based on these data, and 
maintaining a statistical power of 80%, required sample size was adjusted to a total of 34 patients. In 

figure 2, matrices for sample size calculation are shown, based on the cited trial and using 
internationally accepted statistical procedures26. Likewise, in table 3 an output of sample size calculation 
is shown from G*Power 3.1.9.2 (Universität Düsseldorf, Düseldorf, Germany) software27. Finally, 
calculated sample size was increased by 20% in order to avoid study power loss due to drop-outs or 
losses of follow-up. Thus, final sample size was 42 patients, 21 per group. 
 
T test 
Means: Difference between two dependent means (matched pairs) 
Analysis 
A priori: Compute required sample size 
Input 
Tails 
One 
 
Effect size dz 
0,4926108 
 
Α err prob 
0,05 
 
Power (1- β err prob) 
0,8 
Output 
Noncentrality parameter δ 
2,5596808 
 
Critical t 
1,7056179 
 
Degrees of freedom 
26 
 
Total sample size 
27 
 
Actual power 
0,8015888 
McNemar 
Proportions: Inequality, two dependent groups 
Analysis 
A priori: Compute required sample size 
 
Input 
Tails 
Odds ratio 
α 
1- β 
Prop discordant pairs 
One 
3,571 
0,05 
0,8 
0,53782 
Output 
Lower critical N  
Upper critical N 
Total sample size  
Actual power 
Actual α 
Proportion p12 
Proportion p21 
13,0000000 
13,0000000 
34 
0,8169370 
0,0481262 
0,4201608 
0,1176592 
Table 3: Sample size calculation output with G*Power 3.1.9.2 software27 
 
 
Inclusion criteria: 
Patients with GERD who meet with all the following characteristics: 
1. Diagnosis of GERD based on Montreal definition (Esophageal erosions and typical 
symptoms such as pyrosis and/or regurgitation with a frequency ≥ 2 times per week). 
2. Retrosternal pyrosis lasting ≥ 3 months. 
3. Pyrosis and/or regurgitation with a frequency ≥ 3 nights per week 
4. GERD-associated sleep disturbance (insomnia, poor sleep quality) with a frequency ≥ 3 
nights per week, and lasting ≥ 1 month. 
Exclusion criteria: Patients with atypical symptoms and no erosions on endoscopy (NERD: Non-
erosive Gastroesophageal Reflux Disease) will not be included. Likewise, patients with the following 
situations will be excluded from the trial: peptic ulcer, history of biliary surgery, lactating or pregnant 
women, participants under 18 years of age and nighttime shift workers (12 am to 6 am). Patients with 
the following conditions which affect sleep quality will also be excluded: Obstructive sleep apnea 

hypopnea syndrome, chronic obstructive pulmonary disease, patients with nocturnal supplementary 
oxygen requirement, orthopnea, nocturia, restless legs syndrome, patients consuming more than 3 cups 
of coffee per day,  patients planning to travel beyond 3 time zones during study, patients being treated 
with sleep medication (e.g. anxiolytics, antihistamines, benzodiazepines) for less than 3 months or when 
suspension or dose modification of this drugs is being planned during the study course. 
Design and carving of wooden prisms: 124 prisms of withered pine tree wood with dimensions 
20x18x18 cm will be carved from 9 logs of 300x20x20 cm at Aserrío San Ignacio Ltda. production 
plant, located in Soacha, Cundinamarca. Given it is an industrial process of chainsaw cutting and wood 
planning, a quality control will be implemented consisting of verification of prism stability while lying 
on the floor, and the mean height in millimeters of every prism will also be measured and registered. 
Unsteady products or those with atypical mean heights, defined as a height either exceeding percentile 
75 + 1,5 times interquartile range or below percentile 25 – 1,5 times interquartile range, will be 
discarded and not used during the study. As shown in figure 3, this non-pharmacological intervention 
was designed to obtain an inclination range dependent on the bed length of each patient (usually 1,90 
cm in local industry). After exclusion of defective prisms, n groups of wooden prism pairs according to 
mean height in millimeters will be formed and every group will be given a random digit generated by 
computer.  Afterwards, every random digit of prism groups will be sequentially assigned to a 
consecutive HBE-allocated patient number, in such a way that every consecutive patient number 
(among those allocated to HBE) will be linked randomly to a preset known prism height. This 
additional randomization procedure, involving prisms according to their mean height, is planned due to 
the impossibility to guarantee that prism height will be identical with a precision of ±1 mm, keeping in 
mind that products will be cut with chainsaw and will be planed as part of an industrial process. 
 
Improved with treatment A 
Improved with treatment B 
No 
Yes 
Total 
No 
r 
s 
r+s 
Yes 
t 
u 
t+u 
Total 
r+t 
s+t 
N pairs 
 
 
 
Improved with HBE 
Improved without HBE 
No 
Yes 
Total 
No 
29,4% 
11,8% 
41,2% 
Yes 
42% 
16,8% 
58,8% 
Total 
71,4% 
28,6% 
100% 
 
Figure 2: Matrices for sample size calculation, according to reference 20 and 26. HBE: Head of Bed 
Elevation. 
In figure 4, a quality control graph is shown. Mean wooden prism height was a non-normal variable 
when Shapiro-Wilk test was applied (W: 0,908; critical W: 0,979; p: 0.000000). After using predefined 
exclusion rules for atypical values, 2 pairs of wooden prisms were discarded. 

 
Figure 3: Schematic representation of HBE and expected bed inclinations. 
 
Randomization: A list of 42 numbers will be generated, with subsequent binomial transformation, 
by using STATA 13.0 software for Windows (StataCorp LP, Texas, USA) in order to allocate 
participants in a 1:1 proportion to each one of the study arms. Wooden prisms will be marked with a 
consecutive number from 1 to 42 and they will be stored, keeping the marked number out of reach 
from the sight of the researcher in charge of patient recruiting. 
 
Patients that meet the inclusion criteria, have no exclusion criteria and who give written informed 
consent, will be assigned a consecutive number during their outpatient visit according to their order of 
inclusion in the trial. These participants will be randomized to either HBE or control group in the 
moment that a member of the research team verifies, among the stored prisms, the existence of a prism 
pair marked with the same number as the consecutive number assigned to the patient. In the case that 
this pair does exist, then the patient will take home that pair of wooden prisms and use them during the 
first period of the trial according to spoken and written instructions to be given at that moment. On the 
contrary, if a pair of wooden prisms marked with the same consecutive number as the patient, does not 
exist, then it will be understood that the study participant has been allocated to control group during 
the first period of the trial. The member of the research team who verifies the storehouse of wooden 
prisms will not be in charge of confirming inclusion and exclusion criteria and will not assign 
consecutive numbers to patients during outpatient visits. 
 
Allocation concealment: The researcher in charge of confirming inclusion and exclusion criteria, 
fulfilling the Basic Data Formulary and providing the patient with the Informed Consent Format, will 
not be aware of the allocation sequence order until these 3 documents have been applied to the 
participant and a consecutive number has been generated according to their order of inclusion in the 
trial.  After that, a member of the research team in the prism storehouse will verify the existence of a 
prism pair marked with the same number as the consecutive number assigned to the patient, and only 
in that point allocation status of the participant will be known. 
 
 
 

 
Figure 4: Wooden prisms quality control. ICR: Interquartile range; Q1: Quartile 1; Q3: Quartile 3. 
 
Cross-over: After allocation has been completed, patients in the intervention group will receive a 
pair of numbered wooden prisms with dimensions 20x18x18 cm along with written instructions about 
the correct use of the intervention. The patient must sleep with HBE during 6 weeks and both RDQ 
and SF-36 questionnaires will be applied again at the end of this first period while the participant is still 
sleeping with HBE. Afterwards, a washout 2 week period follows in which the participant sleeping with 
HBE will stop using it and will return the pair of wooden prisms to the researchers. After washout 
period has ended and both RDQ and SF-36 questionnaires have been applied again, patients allocated 
to the control group during the first period of the study will receive a random pair of prisms and will be 
instructed to use the prisms for sleeping with HBE during a second period of 6 weeks. Meanwhile, 
participants initially allocated to the HBE group will be followed as a control group in this second 
period of the study. 
 
Blinding: Because HBE is not susceptible to double-blinding, patients allocated to the 
intervention group will always be aware of the group they belong to. However, the researcher in charge 
of statistical analysis of data and writing the results report will work with random-generated alphabetical 
group codes for masking the intervention in each one of the periods of the trial. 
 
Follow-up: After participant allocation, telephonic follow up will be made during both periods of 
the trial with a frequency that is dependent on the intervention group of the patient in that period. 
Participants in the HBE group will be called weekly for 2 weeks, and then will be called biweekly for a 
month, until each period of 6 weeks has ended. In contrast, patients in the control group will be called 
every three weeks along each period. With the purpose of verifying both HBE adherence and correct 
use of wooden prisms, every participant will be asked to send a photograph of the bed head legs during 
the follow-up telephone call. The photograph will be received by the researcher via e-mail or smart-
phone and will be encoded and saved in a hard disk. At the end of the first period, RDQ and SF-36 
questionnaires will be applied and researchers will store the returned prisms during washout period. 
When washout period has ended, RDQ and SF-36 questionnaires will be applied again in order to be 
sure of the absence of any carry-over effect in the group initially allocated to HBE. Finally at week 14, 
RDQ, SF-36 and Patient Preference questionnaires will be administered to complete study ending 
outcome assessments. 
 

In figure 5, a schematic representation of follow-up is shown. 
 
 
 
Figure 5: Schematic representation of photographic and telephonic follow-up. W1-6: Weeks from 1st 
to 6th in each period. 
 
Primary outcome: 
1. Effectiveness: Change of ≥ 0,6 points between basal RDQ questionnaire and the same 
questionnaire administered after 6 weeks of HBE use.  
Secondary outcomes: 
1. Quality of life: Change of ≥ 10 percentage points between basal SF-36 questionnaire and the 
same questionnaire administered after 6 weeks of HBE use. 
2. Patient preference: Proportion of patients who preferred HBE, after finishing 14 weeks of 
the study. 
3. Safety: Proportion of patients with any reported adverse event during HBE or without bed 
inclination. 
Statistic analysis plan: Quantitative and qualitative variables collected with Basic Data Format, RDQ, 
SF-36 and Patient Preference questionnaires will be typed in a Microsoft Excel 2007 database. 
Intervention groups will be masked with an alphabetical code provided by an independent collaborator 
who will not be involved with data analysis or report writing. For statistical processing, database will be 
imported into STATA SE 13.0 for Windows (StataCorp LP, Texas, USA) and descriptive statistics will 
be generated for each variable. Statistically significant differences will be searched for categorical data 
using the Chi-square test or Fisher exact test and normality will be tested for numerical continuous 
variables using the Shapiro-Wilk test. For normally distributed continuous variables, statistically 
significant differences will be searched for by using unpaired Student’s t test. Alternatively, for not 
normally distributed variables Mann-Whitney U test will be applied. For non-normal variables due to 
atypical data, values outside the percentile 50 ± 1,5 interquartile range were excluded. For 
complementary processing of primary outcome and secondary outcome quality of life, score difference 

between periods will be transformed into a binomial variable and a McNemar marginal homogeneity 
test will be applied. McNemar mid-p was used if discordant pairs sum was smaller than 2528. 
Differences with one-tail p<0,05 will be accepted as statistically significant. Exploratory subgroup 
analysis will search for differences stratified according to age group, sex, ethnic group, BMI, 
comorbidities, cups of coffee per day, pharmacological adherence, and length and severity of 
symptoms; among other 16 baseline variables. Subgroup interactions will be tested with Chi-square or 
Fisher exact test, and effect size was expressed as a univariate relative risk from a generalized linear 
model of binomial family. As part of internal quality control of the clinical trial, a pre-test was applied 
to prove the assumption of a negligible carry-over effect, according to expert guidelines29. Analysis of 
variance (ANOVA) for crossover studies was used in search for significant sequence, period and 
treatment effects, assuming a negligible carry-over effect. In the modified intention to treat analysis, 
participants with protocol violations because of bad adherence to HBE, were included, but it was not 
possible to include patients who withdrew from the study because outcome information could not be 
gathered completely. 
Methodology diagram: A schematic representation of the trial methodology is presented in figure 6. 
 
 
 
Figure 6: Schematic representation of the trial methodology. RDQ: Reflux Disease Questionnaire; SF-
36: Short Form 36 Questionnaire; HBE: Head of Bed Elevation; Standard treatment: Based on proton 
pump inhibitors and/or sodium alginate, according to treating physician criteria. 
 
 
 
 
 

WORK TEAM 
Work team of this clinical trial is formed by three authors. The respective roles during the design and 
conduction of the trial, and also the professional profiles of each researcher are described below. 
Researchers: 
• 
Iván Mauricio Villamil Morales (Principal Researcher – study design, patient recruiting, 
telephonic follow-up, outcome assessment, statistical analysis, writing of final report)  
- 
General Practice Physician – Universidad Nacional de Colombia 
- 
3rd year Internal Medicine resident – Universidad Nacional de Colombia 
 
• 
Daniel Mauricio Gallego Ospina(Researcher – patient recruiting, intervention 
administration, clinical and telephonic follow-up, writing of final report)  
- 
General Practice Physician – Universidad Nacional de Colombia 
- 
3rd year Internal Medicine resident – Universidad Nacional de Colombia 
 
• 
William Otero Regino (Researcher and project mentor – study design, critical appraisal 
of study results, writing and correction of final report) 
- 
General Practice Physician – Universidad Nacional de Colombia 
- 
Internal Medicine Specialist – Universidad Nacional de Colombia  
- 
Master of Science in Epidemiology – Universidad del Rosario 
- 
Gastroenterologist – Universidad Nacional de Colombia 
- 
Gastroenterology in Chief – Clínica Fundadores - Bogotá 
 
Researcher’s curriculum vitae (CvLac) can be consulted on-line in the Sistema Nacional de Ciencia y 
Tecnología (Colciencias) platform. 
 
 
ETHICAL AND LEGAL ISSUES 
Regardless of being a randomized controlled clinical trial, the intervention to allocate in the present 
study is not a drug but a non-pharmacological intervention (HBE). Therefore, ethical considerations 
were not based on Resolution 2378 of 2008. 
According to express classification from article 11 from Ministerio de Salud Resolution 8430 of 1993, 
the present study has minimal risk for participants30. No severe or persistent adverse events of HBE 
have been reported in clinical trials published this far16-20. Only one of the cited trials reported 2 adverse 
events, namely: recurrent slipping out of bed without falling and slight sexual problems associated with 
bed position, although they were resolved quickly20. Based on low frequency of these adverse events, 
mildness and rapid resolution, it was not deemed necessary to buy a collective insurance policy to cover 
eventual compensations. Likewise, impartial allocation of participants will be achieved by 
randomization and their safety will be supervised during follow-up. Neither researchers nor patients 
will be exposed to major risks during the trial. 
Alfa-numeric encoding will be implemented in order to protect identity of the participants and 
management of data will be confidential. Any essential change in study protocol, trial conduction or any 
future use of study data will be consulted with Medicine Faculty Ethics Committee at Universidad 
Nacional de Colombia. 

Informed Consent will be provided for all study participants and it will be signed in case of patient 
agreement.  The Informed Consent Format was made according to articles 15 and 16 from Ministerio 
de Salud Resolution 8430 of 1993 (Appendix A). 
Researchers declare no conflicts of interest. If such conflicts emerged during study conduction, they 
will be presented to the Medicine Faculty Ethics Committee at Universidad Nacional de Colombia. 
Likewise, this clinical trial is in accordance with article 13 from Ministerio de Salud Resolution 8430 of 
1993, which highlights research institution responsibility of providing medical care to participants who 
suffer damage directly related to being part of a clinical trial. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

TIMELINE OF ACTIVITIES 
 
  STAGE/ACTIVITY 
Stage I (2 months) 
Stage II (4 months) 
Stage III (1 month) Stage IV (1 month) 
Administrative 
  Protocol writing  
X 
  Faculty Ethics Committee 
X 
X 
  Wooden prism carving  
X 
Data collection 
  Patient sampling 
X 
X 
  Basal questionnaires  
X 
X 
X 
X 
X 
X 
  Post-intervention questionnaires  
X 
X 
X 
X 
X 
X 
  Database consolidation  
X 
X 
X 
X 
X 
X 
X 
X 
Data analysis 
  Statistical analysis  
X 
X 
  Literature review  
X 
X 
  Results discussion  
X 
Results disclosure 
  Preliminary report  
X 
X 
  Final report  
X 
  Public dissertation  
X 
  Original paper writing  
X 
X 
  Submit to publication  
X 
Table 2: Research Project proposed timeline 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

References 
 
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[9] 
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APPENDIX A