Effectiveness of lansoprazole as a treatment of recurrent

abdominal pain among adolescent

Ade Saifan Surya, Selvi Nafianti, Melda Deliana, Supriatmo, Atan Baas Sinuhaji
Department of Child Health, Medical School
University of Sumatera Utara / H. Adam Malik Hospital, Medan

ABSTRACT
Background Recurrent abdominal pain is common among adolescents. School
absenteeism and lower quality of life are indicately associated with the severity of
symptoms. Lansoprazole is assumed to be one of alternative treatment in recurrent
abdominal pain.
Objective To investigate the effectiveness of lansoprazole as a treatment of
recurrent abdominal pain among adolescent.
Methods We conducted a randomized, double blind, controlled trial on August 2009
until October 2009. Adolescents suffering recurrent abdominal pain and met
inclusion criteria were eligibled for the study. Simple randomization done to divided in
two groups. Each group received 30 mg of lansoprazole or placebo once a day for
14 days. Before treatment we performed laboratory and physical examination. Pain
frequency was measured in abdominal pain episode per month, duration was
measured in minutes and pain intensity was measured by pain rating scale. The
efficacy was measured before, during and after intervention. Data was analized
using Mann-Whitney U-test, and t-test.
Results One hundred sixteen recurrent abdominal pain patients were enrolled to the
study, with simple randomization divided in two group with each group had fifty eight
patients. There were no statistically significant differences on the frequency before
and after treatment with lansoprazole and placebo with P=0.083, 95%CI (-0.033 to
0.021) and P=0.096, 95%CI (-0.376 to 0.031), respectively and also frequency,
duration, and degree of abdominal pain at baseline and after 1, 2 and 3 months
treatment between groups.
Conclusion Lansoprazole is not more effective than placebo as the treatment of
recurrent abdominal pain among adolescents.
Key words : lansoprazole, recurrent abdominal pain, adolescent

Introduction

Recurrent abdominal pain (RAP) are abdominal pain attacks, at least three times or
more within a period of three months and effect on activity.1 Incidence ranges from
10% to 20% in school-age children, with peak incidence at age 10 to 12 years and
over often in girls.2,3 Epidemiological study reported 13% to 17% of teenagers
experiencing abdominal pain every week, where 20% of incident is quite heavy and
affects activity.4 One study in Malaysia reported incidence rate of 10.2% in school
age children.5
Recurrent abdominal pain is presumably caused by organic or functional
disorders. Although organic disorder should be considered, however, the cause is
only found less than 10% patients. Functional abdominal pain is characterized by
abdominal pain in the umbilicus and usually accompanied by symptoms such as
nausea, vomiting, dizziness, pale and headache.6,7 Several studies have reported
that RAP reduces quality of life, sleep disorders, visit to child health services,
declining academic achievement and significantly increasing the number of
absences in school.8-10
Clinical trials have suggested benefits of H 2-receptor antagonist significantly
reduced the frequency, severity of RAP accompanied by symptoms dyspepsia. 11
Proton pump inhibitor (PPI) lansoprazole reported has a better efficacy than H 2receptor

antagonist

in

reducing

gastric

acid

secretion

and

treatment

of

gastrointestinal ulcers, and esophagitis in some study.12,13 This study was designed to
investigate the effectiveness of lansoprazole as a treatment of recurrent abdominal
pain among adolescent.
Methods
We conducted a randomized double-blind controlled trial from August to October
2009, at five junior/senior high school in Langkat district. Adolescents with a history
of abdominal pain and met inclusion criteria were eligibled for the study. Our
inclusion criteria were adolescents aged 12 to 18 years, met diagnostic criteria for
RAP (Apleys criteria), and good nutritional status. The exclusion criteria were
patients using other drugs as incurred of abdominal pain, malnutrition, chronic
diarhea, constipation, bloody stools, urinary tract infection, anemia, parasitic infection
and dysmenorrhea.
We divided patients into two groups. Simple randomization using envelope of
random numbers was used to assign 58 patients to lansoprazole or placebo. Group I
2

who received 30 mg of lansoprazole once daily in the morning, given for fourteen
days and placebo in group II. Firstly, a questionnaire was used to identify
adolescents suffering from RAP, to established the frequency, duration and severity
of the pain. Pain frequency was measured in abdominal pain episode per month,
duration was measured in minute and the severity of pain was measured with pain
rating scales (0= no pain, 10= awful pain) and stratification was determined
according to the severity of the pain (mild 0-3; moderate 4-6; severe 7-10). We
collected the frequency, duration and severity of the pain from each group with a
daily diary which given every month for 3 months.
We measured anthropometric value from each patient before the study
began. We performed each patient weight and height. Weight was measured used
pair of scales Camry (sensitivity 0.1 Kg) and height was measured used stature
meter 2M (sensitivity 0.5 cm). Nutritional stages was done depended on body weight
(BW) per body height (BH) BW/BH (%), then the value we plot on the Centers for
disease control and prevention (CDC) growth charts 2000. Obesity was mentioned if
the BW/BH 120%, overweight if the BW/BH 110% - < 120%, good nutritional status
BW/BH 90% - < 110%, underweight if the BW/BH 70% - < 90% and poor nutritional
status BW/BH < 70%. We performed physical and laboratory examination. Blood
tests performed using Sahli hemoglobine, urine with urine dipstick verivy and stool
examination by Kato Katz method.
Both lansoprazole and placebo were packed in similar color and shape
capsules. Researchers and patients didnt know which drugs were given. If
abdominal pain still continues, patients are allowed to take medication of
paracetamol 500 mg every 8 hours. The patient were writing informed consent
before the study began. This study was approved by Research Ethics Committee of
Medical School, University of Sumatera Utara.
The collection data was being processed, analyzed and presented using the
Statistical Package for the Social Sciences (Windows version 15.0; SPSS Inc,
Chicago). Analysis of data to assess the frequency of pain used t test. Severity and
duration of pain used Mann-Whitney U-test. Each data were writing in 95%
confidence interval and level of significant P<0.05 and overall analysis using the
intention-to-treat.
Result

We investigated 820 students, and found 228 students with RAP, of whom 66
patients did not meet inclusion criteria and 46 of them refused to participate in this
study, while the remaining 116 children were included in the study. Each group
contents 58 students who received lansoprazole or placebo. After three months
follow up, there were no drop out from each group. (Figure 1)

820 students screened

228 abdominal pain

66 did not met criteria inclusion

46 refused

RAP
N=116

Lansoprazole
n = 58

Placebo
n = 58

Participated in this study

and follow up over
3 months
n=58

Participated in this study

and follow up over
3 months
n=58

Figure 1. Study profile

Table 1. Baseline characteristic

4

Lansoprazole

Placebo

n=58
13.2 (0.85)

n=58
13.8 (1.63)

Male

23(19.83)

25(21.55)

Female

35(30.17)

33(28.44)

Body weight (kg), mean (SD)

36.7 (4.50)

40.5 (7.60)

Body height (cm), mean (SD)

145.1 (5.80)

147.0 (8.10)

BW/BH (%), mean (SD)

97.6 (8.31)

99.3 (13.08)

Hemoglobine (g/dL), mean (SD)

12.4(0.87)

12.5 (0.76)

15 (12.93)

8 (6.89)

37 (31.89)

42 (36.2)

6 (5.17)

8 (6.89)

Primary school

3 (2.58)

3 (2.58)

Junior high school

13 (11.2)

10 (8.62)

Senior high school

32 (27.58)

36 (31.03)

Scholar

10 (8.62)

9 (7.75)

Characteristic
Age (years), mean (SD)
Sex, n (%)

Parental income, n (%)

< Rp. 500.000
Rp. 500.000 1.000.000
> Rp. 1.000.000

17

Parent education, n (%)

Associated symptoms, n (%)

Headache

7 (6.03)

9 (7.75)

Nausea and vomiting

10 (8.62)

13 (11.2)

Joint pain

2 (1.72)

3 (2.58)

33(28.44)

37(31.89)

Upper abdomen

13(11.2)

25(21.55)

Lower abdomen

3(2.58)

5(4.31)

Consultation, n (%)

4(3.44)

3(2.58)

Location of pain, n (%)

Periumbilicus

Average age in lansoprazole group was 13.2 years and placebo group was
13.8 years. Female was more often found in both group. Nutritional status based on
the BW/BH in both groups within the normal range and also hemoglobine
concentration with an average of 12 g/dL. Most parents income was between 500
thousand to 1 million rupiah per month and the highest educational level was high
school. The most common associated symptoms were nausea and vomiting has
been reported in both groups. The location of abdominal pain on periumbilical was
reported by 33 (28.44%) and 37 (31.89%) students in lansoprazole and placebo
group respectively. Only 6% of students visits to health services was reported.
Table 2. Frequency of pain before and after treatment
5

Lansoprazole
Placebo

Before
5.9 (1.17)
5.4 (1.31)

After
5.8 (1.11)
5.2 (1.48)

95% CI
-0.331;0.021
-0.376;0.031

P
0.083
0.096

Value in mean (SD)

In Table 2, decreased frequency of RAP in adolescents was not significantly

different before and after treatment with both lansoprazole or placebo during 3
months observation.
Table 3. Frequency of pain between lansoprazole and placebo
Lansoprazole

Placebo

95% CI

At baseline

5.9 (1.17)

5.4 (1.31)

(0.113;1.025)

0.081

After 3 months

5.8 (1.109)

5.2 (1.48)

(0.105;1.0677)

0.064

1 month

2.0 (0.65)

1.8 (0.53)

(-0.028;0.4076)

0.087

2 months

1.9 (0.51)

1.7 (0.60)

(-0.016;0.3954)

0.071

3 months
Value in mean (SD)

1.9 (0.539)

1.7 (0.59)

(-0.017;0.3968)

0.072

Our data also found no statistically significant differences on the mean

frequency of RAP in adolescents between lansoprazole and placebo groups at the
baseline. Similarly, the average frequency of RAP during months 1, 2 and 3 of
treatment with lansoprazole compared to placebo.

Table 4. Duration before and after received treatment

Duration of pain

Lansoprazole

Placebo

At baseline

1 month

2 months

3 months

(minute)

n (%)

n (%)

< 10

20 (17.2)

33 (28.4)

10-30

33 (28.4)

17 (14.7)

30-60

4 (3.4)

8 (6.9)

> 60

1 (0.9)

< 10

15 (12.9)

31 (26.7)

10-30

39 (33.6)

17 (14.7)

30-60

4 (3.4)

10 (8.6)

> 60

< 10

23 (19.8)

37 (31.9)

10-30

32 (27.6)

13 (11.2)

30-60

3 (2.6)

8 (6.9)

> 60

< 10

32 (27.6)

44 (37.9)

10-30

22 (19.0)

7 (6.0)

30-60

4 (3.4)

7 (6.0)

> 60

0.076

0.065

0.067

0.060

The duration of pain on lansoprazole and placebo groups at the beginning of

observation, was not found significant differences. Similarly, duration of pain after 1
month, 2 months and 3 months treatment showed no significant differences. (Table
4).

Tabel 5. Degree of pain before and after received treatment

Degree of pain

Lansoprazole

Placebo

n (%)

n (%)

At baseline

Mild

28 (24.1)

39 (33.6)

Moderate

26 (22.4)

15 (12.9)

4 (3.4)

4 (3.4)

Mild

23 (19.8)

36 (31.0)

Moderate

31 (26.7)

16 (13.8)

4 (3.4)

6 (5.2)

Mild

29 (25.0)

39 (33.6)

Moderate

25 (21.6)

16 (13.8)

4 (3.4)

3 (2.6)

Mild

29 (25.0)

40 (34.5)

Moderate

25 (21.6)

14 (12.1)

4 (3.4)

4 (3.4)

Severe

1 month

Severe
2 months

Severe
3 months

Severe

0.060

0.051

0.070

0.058

There were no reductions in degree of pain in both groups after the end of
study. There were no statistically differences in both groups. (Table 5)
Discussion
This present study conducted in rural areas in Langkat district, which found the
average income of parents, including low-income groups with an average high
school education. The study also indicate that the prevalence of recurrent abdominal
pain (RAP) is still quite high, amounting to 27.8%, with an average age of 13.2 years
in lansoprazole group and 13.8 years in the placebo group. Lower prevalence
between 0.3% to 19% was described by a systematic review in western countries 14,
but the other study in Malaysia found the prevalence of RAP in a rural school
showed a higher rate of 41.2% with lower parent education. 15 An American study
involving 507 adolescents, have an average age of patients 12.6 years for junior high
and high school students 15.6 years, where the abdominal pain experienced by 13%
to 17% and interfere the activities on 21% adolescents. 16
Our study found RAP was more frequently present on adolescent girls
(58.6%) compared with adolescent males (41.4%). Similarly, a cohort study done in
Sri Langka reported a higher incidence in girls. 17 The incidence shows similarly

between girls and boys up to age 9 years. After 9 years of increasing incidence in
girls, with the ratio of male : female was 1:1.5. 3
More than half of the students (60%) in this study, showing locations of pain in
the periumbilical region, this shows the same results with several previous studies in
Australia and Bangladesh.18,19 RAP may be accompanied by symptoms such as
headache, nausea, vomiting and joint pain. 19,20 On our study, we found symptoms of
headache, nausea and vomiting, and joint pain in the patients.
Visits of medication in health care or the physician give varying figures. We
only reported 6% of patients came to medical visits seeking medication in the last
three months. Higher visiting were reported in studies in the United States on 8% of
patients.16 While study in Australia reported 34% visits. 18 Study in Malaysia reported
45% and 48% of visits.20,21
Malnutrition and anemia associated with RAP were an alarm signal (red flags)
which leads us to determine organic disorder as the underlying cause. 3 The
presence of alarm symptoms requires us to further investigation. 22,23 Depending on
malnutrition and anemia, this study takes the inclusion criteria that patients with good
nutritional status and do not suffer from anemia, whereas in the both sample of
group show BW/BH were 90% to < 110 %, and hemoglobin level 12 g / dL.
Lansoprazole is a class of proton pump Inhibitors (PPIs) is a substituted
benzimidazole which is lipophilic weak bases, that cross the membrane and enter
into canaliculus parietal cells. In this acidic environment, the PPIs will be activated to
sulphenamide form that binds covalently with H +, K +- adenosine triphosphatase
enzyme that inhibition acid secretion by the proton pump. 24,25 One study reported
lansoprazole is effective and safe in children with reflux oesophagitis and the optimal
starting dosage is 30 mg/m2 or 1.4 mg/kg,26 but study on the use of lansoprazole as
RAP treatment has not been reported previously.
The initial examination of the frequency, duration and levels of abdominal pain
in adolescents found no significant difference between the two groups, as well as the
examination after 1 month to 3 months got the treatment. A difference results found
with previous studies with famotidine, because no assessment of the symptoms of
dyspepsia in our study.
There were some limitations noted in our study, such as diagnostic criteria for
RAP using Apleys criteria are often considered too boarded in assessing the specific
disorders of RAP, whereas the use of Rome criteria provide a clearer operational
9

limits, just that its use is still very slight in research. In addition, lack of supervision of
compliance of patient takes a drug that has been given. Monitoring is only performed
on the number of drugs given to sufferers, this is indicated by the absence of drugs
returned by patients during the study was conducted. Some aspects of the
assessment of the duration and highly subjective pain level of each patient.
Conclusion
Our study concluded that treatment using lansoprazole with a dose of 30 mg given
once a day for 14 days in adolescents with RAP, showed no significant differences in
frequency before and after treatment. Treatment with lansoprazole also showed no
significant differences on the frequency, duration and degree of abdominal pain in
adolescents compared to placebo.
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