Trial Outcomes & Findings for Anxiety and Recurrent Abdominal Pain in Children (NCT NCT00962039)

NCT ID: NCT00962039

Last Updated: 2020-06-11

Results Overview

Clinical Global Impression Scale - Improvement (CGI-I) is a 7-point scale, with lower values being more favorable, used to assess overall global illness improvement. The CGI is a clinician-completed measure, with values ranging from 1 (very much improved), 2 (much improved), 3 (minimally improved), 4 (no change), 5 (minimally worse), 6 (much worse), to 7 (very much worse). CGI-I scores of 1 (very much improved) or 2 (much improved) were considered to indicate an acceptable treatment response. A global measure of functional status was chosen as a primary outcome due to the broad array of symptomatology seen in pediatric RAP and the ambiguous relationship between functional status and symptoms of pain, anxiety, and depression in pediatric RAP. The CGI-I is a dichotomous primary outcome measure of global clinical improvement with clinical response be defined as a CGI-I score of 1 or 2 for at least two consecutive weeks.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

81 participants

Primary outcome timeframe

The CGI will be completed at weeks 2, 4, and 8

Results posted on

2020-06-11

Participant Flow

Subjects were clinically referred from primary care and specialty pediatric gastroenterology and were impaired as reflected by a score of less than 70 on the Children's Global Assessment Scale (CGAS).

Potential subjects with physical disease responsible for the abdominal pain, eating disorder, bipolar disorder, psychosis, alcohol/drug abuse, intellectual disability (IQ \< 70), pregnancy, or prior trial of SSRI antidepressant or venlafaxine were excluded.

Participant milestones

Participant milestones
Measure
Citalopram
Citlaopram: Participants were randomly assigned to citalopram or placebo in a parallel groups design for 8 weeks of double-blind treatment beginning with 10 mg per day week 1, 20 mg per day week 2, and 40 mg per day week 4 or thereafter if response was suboptimal and there were no significant side effects.
Placebo
Placebo: Participants were randomly assigned to citalopram or placebo in a parallel groups design for 8 weeks of double-blind treatment beginning with 10 mg per day week 1, 20 mg per day week 2, and 40 mg per day week 4 or thereafter if response was suboptimal and there were no significant side effects.
Overall Study
STARTED
40
41
Overall Study
COMPLETED
35
37
Overall Study
NOT COMPLETED
5
4

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Anxiety and Recurrent Abdominal Pain in Children

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Citalopram
n=40 Participants
This double blind, placebo-controlled trial randomized 81 subjects ages 7 to 18 years in parallel groups to citalopram (n=40) or placebo (n=41) for 8 weeks. Citalopram was initiated at 10 mg per day week 1, 20 mg per day week 2, and 40 mg per day week 4 or thereafter if response was suboptimal and there were no significant side effects. Subjects were recruited by clinical referral from both the primary care and specialty pediatric gastroenterology clinical settings. In addition to meeting criteria for FAP, subjects were required to be significantly impaired as reflected by a score of less than 70 on the Children's Global Assessment Scale (CGAS). Potential subjects with physical disease responsible for the observed abdominal pain, eating disorder, bipolar disorder, psychosis, alcohol/drug abuse, intellectual disability (IQ \< 70), pregnancy, or prior trial of SSRI antidepressant or venlafaxine were excluded.
Placebo
n=41 Participants
This double blind, placebo-controlled trial randomized 81 subjects ages 7 to 18 years in parallel groups to citalopram (n=40) or placebo (n=41) for 8 weeks. Citalopram was initiated at 10 mg per day week 1, 20 mg per day week 2, and 40 mg per day week 4 or thereafter if response was suboptimal and there were no significant side effects. Subjects were recruited by clinical referral from both the primary care and specialty pediatric gastroenterology clinical settings. In addition to meeting criteria for FAP, subjects were required to be significantly impaired as reflected by a score of less than 70 on the Children's Global Assessment Scale (CGAS). Potential subjects with physical disease responsible for the observed abdominal pain, eating disorder, bipolar disorder, psychosis, alcohol/drug abuse, intellectual disability (IQ \< 70), pregnancy, or prior trial of SSRI antidepressant or venlafaxine were excluded.
Total
n=81 Participants
Total of all reporting groups
Age, Categorical
<=18 years
40 Participants
n=5 Participants
41 Participants
n=7 Participants
81 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Age, Categorical
>=65 years
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Sex: Female, Male
Female
29 Participants
n=5 Participants
33 Participants
n=7 Participants
62 Participants
n=5 Participants
Sex: Female, Male
Male
11 Participants
n=5 Participants
8 Participants
n=7 Participants
19 Participants
n=5 Participants

PRIMARY outcome

Timeframe: The CGI will be completed at weeks 2, 4, and 8

Population: Analysis week 8

Clinical Global Impression Scale - Improvement (CGI-I) is a 7-point scale, with lower values being more favorable, used to assess overall global illness improvement. The CGI is a clinician-completed measure, with values ranging from 1 (very much improved), 2 (much improved), 3 (minimally improved), 4 (no change), 5 (minimally worse), 6 (much worse), to 7 (very much worse). CGI-I scores of 1 (very much improved) or 2 (much improved) were considered to indicate an acceptable treatment response. A global measure of functional status was chosen as a primary outcome due to the broad array of symptomatology seen in pediatric RAP and the ambiguous relationship between functional status and symptoms of pain, anxiety, and depression in pediatric RAP. The CGI-I is a dichotomous primary outcome measure of global clinical improvement with clinical response be defined as a CGI-I score of 1 or 2 for at least two consecutive weeks.

Outcome measures

Outcome measures
Measure
Citalopram
n=40 Participants
Citalopram was initiated at 10 mg daily for one week, with dosage increased to 20 mg daily during week 2, with an optional increase to 40 mg daily at week 4 or thereafter if response was judged to be suboptimal (CGI-I or CGI-S \> 2). Citalopram: Participants will be randomly assigned to citalopram or placebo in a parallel groups design for 8 weeks of double-blind treatment beginning with 10 mg per day week 1, 20 mg per day week 2, and 40 mg per day week 4 or thereafter if response is suboptimal and there are no significant side effects.
Placebo
n=41 Participants
Placebo administered in capsules identical to those containing citalopram using microcrystalline cellulose. Placebo: Participants will be randomly assigned to citalopram or placebo in a parallel groups design for 8 weeks of double-blind treatment beginning with 10 mg per day week 1, 20 mg per day week 2, and 40 mg per day week 4 or thereafter if response is suboptimal and there are no significant side effects.
Clinical Global Impression Scale - Improvement (CGI-I) Will be Used to Assess Overall Global Illness Improvement. CGI-I Scores of 1 (Very Much Improved) or 2 (Much Improved) Indicate an Acceptable Treatment Response.
CGI-I Week 4
3.03 units on a scale
Interval 2.78 to 3.28
3.38 units on a scale
Interval 3.09 to 3.67
Clinical Global Impression Scale - Improvement (CGI-I) Will be Used to Assess Overall Global Illness Improvement. CGI-I Scores of 1 (Very Much Improved) or 2 (Much Improved) Indicate an Acceptable Treatment Response.
CGI-I Week 8
2.65 units on a scale
Interval 2.23 to 3.07
3.24 units on a scale
Interval 2.88 to 3.61
Clinical Global Impression Scale - Improvement (CGI-I) Will be Used to Assess Overall Global Illness Improvement. CGI-I Scores of 1 (Very Much Improved) or 2 (Much Improved) Indicate an Acceptable Treatment Response.
CGI-I Week 2
3.48 units on a scale
Interval 3.25 to 3.72
3.68 units on a scale
Interval 3.44 to 3.93

PRIMARY outcome

Timeframe: Weeks 0, 2, 4, and 8

Population: Analysis week 8

Clinical Global Impression Scale - Severity (CGI-S) is a 7-point scale is a clinician-completed measure that requires the clinician to rate the severity of the patient's illness at the time of assessment relative to the clinician's past experience with patients who have the same diagnosis. Considering total clinical experience, a patient is assessed on severity of illness at the time of rating, with values ranging from 1 (normal, not at all ill), 2 (borderline ill), 3 (mildly ill), 4 (moderately ill), 5 (markedly ill), 6 (severely ill), to 7 (extremely ill).

Outcome measures

Outcome measures
Measure
Citalopram
n=40 Participants
Citalopram was initiated at 10 mg daily for one week, with dosage increased to 20 mg daily during week 2, with an optional increase to 40 mg daily at week 4 or thereafter if response was judged to be suboptimal (CGI-I or CGI-S \> 2). Citalopram: Participants will be randomly assigned to citalopram or placebo in a parallel groups design for 8 weeks of double-blind treatment beginning with 10 mg per day week 1, 20 mg per day week 2, and 40 mg per day week 4 or thereafter if response is suboptimal and there are no significant side effects.
Placebo
n=41 Participants
Placebo administered in capsules identical to those containing citalopram using microcrystalline cellulose. Placebo: Participants will be randomly assigned to citalopram or placebo in a parallel groups design for 8 weeks of double-blind treatment beginning with 10 mg per day week 1, 20 mg per day week 2, and 40 mg per day week 4 or thereafter if response is suboptimal and there are no significant side effects.
Clinical Global Impression Scale - Severity (CGI-S)
CGI-S Week 0
4.31 units on a scale
Interval 3.93 to 4.69
4.39 units on a scale
Interval 4.14 to 4.64
Clinical Global Impression Scale - Severity (CGI-S)
CGI-S Week 2
3.83 units on a scale
Interval 3.45 to 4.21
4.03 units on a scale
Interval 3.7 to 4.35
Clinical Global Impression Scale - Severity (CGI-S)
CGI-S Week 4
3.56 units on a scale
Interval 3.25 to 3.87
3.86 units on a scale
Interval 3.54 to 4.19
Clinical Global Impression Scale - Severity (CGI-S)
CGI-S Week 8
2.76 units on a scale
Interval 2.38 to 3.13
3.51 units on a scale
Interval 3.07 to 3.96

PRIMARY outcome

Timeframe: Weeks 0, 2, 4, and 8

Population: Analysis week 8

The API is a well-validated and reliable measure of abdominal pain assessing the frequency, duration, and intensity of abdominal pain consisting of five items assessing the frequency, duration, and intensity of abdominal pain experienced during the prior 2 weeks. Two of the items are scored from 0 to 5, one is scaled 0 to 8, and two are scaled 0 to 10, with lower scores considered to be better than higher scores. Item scores are standardized using Z-scores and then summed to yield an index of abdominal pain that has been sensitive to change in previous epidemiological and treatment studies of FAP. Alpha reliability ranged from 0.80 to 0.93. The API will be a continuous primary outcome measure of abdominal pain.

Outcome measures

Outcome measures
Measure
Citalopram
n=40 Participants
Citalopram was initiated at 10 mg daily for one week, with dosage increased to 20 mg daily during week 2, with an optional increase to 40 mg daily at week 4 or thereafter if response was judged to be suboptimal (CGI-I or CGI-S \> 2). Citalopram: Participants will be randomly assigned to citalopram or placebo in a parallel groups design for 8 weeks of double-blind treatment beginning with 10 mg per day week 1, 20 mg per day week 2, and 40 mg per day week 4 or thereafter if response is suboptimal and there are no significant side effects.
Placebo
n=41 Participants
Placebo administered in capsules identical to those containing citalopram using microcrystalline cellulose. Placebo: Participants will be randomly assigned to citalopram or placebo in a parallel groups design for 8 weeks of double-blind treatment beginning with 10 mg per day week 1, 20 mg per day week 2, and 40 mg per day week 4 or thereafter if response is suboptimal and there are no significant side effects.
Abdominal Pain Index (API)
API-C Week 2
-0.14 score on a scale
Interval -0.43 to 0.14
0.06 score on a scale
Interval -0.19 to 0.31
Abdominal Pain Index (API)
API-C Week 4
-0.21 score on a scale
Interval -0.5 to 0.08
0.08 score on a scale
Interval -0.2 to 0.36
Abdominal Pain Index (API)
API-C Week 8
-0.36 score on a scale
Interval -0.65 to -0.06
-0.03 score on a scale
Interval -0.34 to 0.27
Abdominal Pain Index (API)
API-C Week 0
0.45 score on a scale
Interval 0.2 to 0.69
0.47 score on a scale
Interval 0.27 to 0.68

SECONDARY outcome

Timeframe: Weeks 0, 2, 4, and 8

Population: Analysis week 8

Pediatric Anxiety Rating Scale (PARS) is a clinician administered measure of anxiety in children and adolescents. The PARS is comprised of a 50-item symptom checklist used to determine the presence or absence of specific anxiety symptoms during the prior week and 7 severity/impairment items, each scored from 0 to 5 . The the score on the 7 items allows the clinician to rate symptom severity and associated impairment on a range from 0 to 35, with higher scores reflecting greater symptom severity and associated impairment. The PARS is characterized by high interrater reliability (ICC = 0.97), adequate internal consistency (α = 0.64), and fair test-retest reliability (ICC = 0.55). There is preliminary support for convergent and divergent validity, and the PARS has demonstrated sensitivity to treatment effects in previously conducted clinical trials.

Outcome measures

Outcome measures
Measure
Citalopram
n=40 Participants
Citalopram was initiated at 10 mg daily for one week, with dosage increased to 20 mg daily during week 2, with an optional increase to 40 mg daily at week 4 or thereafter if response was judged to be suboptimal (CGI-I or CGI-S \> 2). Citalopram: Participants will be randomly assigned to citalopram or placebo in a parallel groups design for 8 weeks of double-blind treatment beginning with 10 mg per day week 1, 20 mg per day week 2, and 40 mg per day week 4 or thereafter if response is suboptimal and there are no significant side effects.
Placebo
n=41 Participants
Placebo administered in capsules identical to those containing citalopram using microcrystalline cellulose. Placebo: Participants will be randomly assigned to citalopram or placebo in a parallel groups design for 8 weeks of double-blind treatment beginning with 10 mg per day week 1, 20 mg per day week 2, and 40 mg per day week 4 or thereafter if response is suboptimal and there are no significant side effects.
Pediatric Anxiety Rating Scale (PARS)
PARS Week 8
2.69 units on a scale
Interval 1.66 to 3.73
5.55 units on a scale
Interval 3.71 to 7.39
Pediatric Anxiety Rating Scale (PARS)
PARS Week 4
2.57 units on a scale
Interval 1.55 to 3.59
5.76 units on a scale
Interval 3.79 to 7.72
Pediatric Anxiety Rating Scale (PARS)
PARS Week 0
7.38 units on a scale
Interval 5.66 to 9.11
9.73 units on a scale
Interval 7.76 to 11.7
Pediatric Anxiety Rating Scale (PARS)
PARS Week 2
4.00 units on a scale
Interval 2.81 to 5.19
6.78 units on a scale
Interval 4.8 to 8.75

SECONDARY outcome

Timeframe: Weeks 0, 2, 4, and 8

Population: Analysis week 8

Children's Depression Rating Scale - Revised (CDRS-R) is a clinician administered measure of depression in children and adolescents and provides data necessary to diagnose depressive disorder and rate the severity of depressive symptoms over time. The CDRS-R is composed of 17 items, most rated on a 1 to 7 scale, with a minimum score of 17 and a maximum of 113. Higher scores reflect greater depression severity, with scores of 40 and above generally considered to be reflective of a depressive diagnosis.

Outcome measures

Outcome measures
Measure
Citalopram
n=40 Participants
Citalopram was initiated at 10 mg daily for one week, with dosage increased to 20 mg daily during week 2, with an optional increase to 40 mg daily at week 4 or thereafter if response was judged to be suboptimal (CGI-I or CGI-S \> 2). Citalopram: Participants will be randomly assigned to citalopram or placebo in a parallel groups design for 8 weeks of double-blind treatment beginning with 10 mg per day week 1, 20 mg per day week 2, and 40 mg per day week 4 or thereafter if response is suboptimal and there are no significant side effects.
Placebo
n=41 Participants
Placebo administered in capsules identical to those containing citalopram using microcrystalline cellulose. Placebo: Participants will be randomly assigned to citalopram or placebo in a parallel groups design for 8 weeks of double-blind treatment beginning with 10 mg per day week 1, 20 mg per day week 2, and 40 mg per day week 4 or thereafter if response is suboptimal and there are no significant side effects.
Children's Depression Rating Scale - Revised (CDRS-R)
CDRS-R Week 2
27.81 units on a scale
Interval 24.76 to 30.86
31.89 units on a scale
Interval 27.8 to 35.99
Children's Depression Rating Scale - Revised (CDRS-R)
CDRS-R Week 4
24.97 units on a scale
Interval 22.31 to 27.62
28.35 units on a scale
Interval 25.01 to 31.69
Children's Depression Rating Scale - Revised (CDRS-R)
CDRS-R Week 0
34.50 units on a scale
Interval 30.32 to 38.68
39.23 units on a scale
Interval 35.02 to 43.44
Children's Depression Rating Scale - Revised (CDRS-R)
CDRS-R Week 8
23.88 units on a scale
Interval 21.17 to 26.6
28.39 units on a scale
Interval 23.32 to 33.47

SECONDARY outcome

Timeframe: Weeks 0, 2, 4, and 8

Population: Analysis week 8

Children's Global Assessment Scale (C-GAS) is an interview-based adaptation of the Global Assessment Scale developed to assess child and adolescent functioning during a specified time period. Scores range from one to 100, with scores of 70 or below reflecting abnormally low functioning and higher scores reflecting better functioning. The C-GAS has demonstrated reliability, as well as discriminant and concurrent validity. A CGAS score of \< 70 will be a requirement at study entry.

Outcome measures

Outcome measures
Measure
Citalopram
n=40 Participants
Citalopram was initiated at 10 mg daily for one week, with dosage increased to 20 mg daily during week 2, with an optional increase to 40 mg daily at week 4 or thereafter if response was judged to be suboptimal (CGI-I or CGI-S \> 2). Citalopram: Participants will be randomly assigned to citalopram or placebo in a parallel groups design for 8 weeks of double-blind treatment beginning with 10 mg per day week 1, 20 mg per day week 2, and 40 mg per day week 4 or thereafter if response is suboptimal and there are no significant side effects.
Placebo
n=41 Participants
Placebo administered in capsules identical to those containing citalopram using microcrystalline cellulose. Placebo: Participants will be randomly assigned to citalopram or placebo in a parallel groups design for 8 weeks of double-blind treatment beginning with 10 mg per day week 1, 20 mg per day week 2, and 40 mg per day week 4 or thereafter if response is suboptimal and there are no significant side effects.
Children's Global Assessment Scale (C-GAS)
CGAS Week 0
54.42 units on a scale
Interval 51.95 to 56.89
54.07 units on a scale
Interval 51.77 to 56.38
Children's Global Assessment Scale (C-GAS)
CGAS Week 2
59.24 units on a scale
Interval 55.98 to 62.49
58.05 units on a scale
Interval 54.61 to 61.49
Children's Global Assessment Scale (C-GAS)
CGAS Week 4
63.27 units on a scale
Interval 60.05 to 66.5
59.14 units on a scale
Interval 56.1 to 62.17
Children's Global Assessment Scale (C-GAS)
CGAS Week 8
66.72 units on a scale
Interval 62.74 to 70.7
61.22 units on a scale
Interval 57.47 to 64.97

Adverse Events

Citalopram

Serious events: 0 serious events
Other events: 31 other events
Deaths: 0 deaths

Placebo

Serious events: 0 serious events
Other events: 36 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Citalopram
n=40 participants at risk
Citlaopram: Participants were randomly assigned to citalopram or placebo in a parallel groups design for 8 weeks of double-blind treatment beginning with 10 mg per day week 1, 20 mg per day week 2, and 40 mg per day week 4 or thereafter if response was suboptimal and there were no significant side effects.
Placebo
n=41 participants at risk
Placebo: Participants were randomly assigned to citalopram or placebo in a parallel groups design for 8 weeks of double-blind treatment beginning with 10 mg per day week 1, 20 mg per day week 2, and 40 mg per day week 4 or thereafter if response was suboptimal and there were no significant side effects.
Gastrointestinal disorders
gastric distress
32.5%
13/40 • 8 weeks
34.1%
14/41 • 8 weeks
Metabolism and nutrition disorders
appetite or weight change
27.5%
11/40 • 8 weeks
48.8%
20/41 • 8 weeks
Eye disorders
vision disturbance
5.0%
2/40 • 8 weeks
7.3%
3/41 • 8 weeks
Nervous system disorders
dizziness
40.0%
16/40 • 8 weeks
39.0%
16/41 • 8 weeks
Nervous system disorders
headache
77.5%
31/40 • 8 weeks
87.8%
36/41 • 8 weeks
Skin and subcutaneous tissue disorders
itching
27.5%
11/40 • 8 weeks
19.5%
8/41 • 8 weeks
General disorders
fatigue
50.0%
20/40 • 8 weeks
68.3%
28/41 • 8 weeks
Gastrointestinal disorders
nausea or vomiting
52.5%
21/40 • 8 weeks
58.5%
24/41 • 8 weeks
General disorders
body aches
72.5%
29/40 • 8 weeks
75.6%
31/41 • 8 weeks
Cardiac disorders
palpitations
30.0%
12/40 • 8 weeks
29.3%
12/41 • 8 weeks
Gastrointestinal disorders
bowel movement disturbance
50.0%
20/40 • 8 weeks
51.2%
21/41 • 8 weeks
Eye disorders
eye irritation
7.5%
3/40 • 8 weeks
4.9%
2/41 • 8 weeks
General disorders
dry mouth
12.5%
5/40 • 8 weeks
4.9%
2/41 • 8 weeks
Ear and labyrinth disorders
earache
12.5%
5/40 • 8 weeks
9.8%
4/41 • 8 weeks
General disorders
nosebleed
10.0%
4/40 • 8 weeks
9.8%
4/41 • 8 weeks
Ear and labyrinth disorders
hearing disturbance
12.5%
5/40 • 8 weeks
9.8%
4/41 • 8 weeks
General disorders
throat pain
27.5%
11/40 • 8 weeks
24.4%
10/41 • 8 weeks
Nervous system disorders
motor disturbances (tics, twitches)
12.5%
5/40 • 8 weeks
7.3%
3/41 • 8 weeks
Renal and urinary disorders
urinary disturbance
17.5%
7/40 • 8 weeks
24.4%
10/41 • 8 weeks
Infections and infestations
upper respiratory infection
25.0%
10/40 • 8 weeks
26.8%
11/41 • 8 weeks
General disorders
sweating
5.0%
2/40 • 8 weeks
4.9%
2/41 • 8 weeks
General disorders
accidental injuries
7.5%
3/40 • 8 weeks
4.9%
2/41 • 8 weeks
Nervous system disorders
hyperactive
27.5%
11/40 • 8 weeks
43.9%
18/41 • 8 weeks
Psychiatric disorders
aggression
7.5%
3/40 • 8 weeks
2.4%
1/41 • 8 weeks
Psychiatric disorders
nightmares
10.0%
4/40 • 8 weeks
2.4%
1/41 • 8 weeks
Psychiatric disorders
irritability
20.0%
8/40 • 8 weeks
41.5%
17/41 • 8 weeks
General disorders
sleep disturbance
52.5%
21/40 • 8 weeks
68.3%
28/41 • 8 weeks
Psychiatric disorders
anxiety and panic
17.5%
7/40 • 8 weeks
36.6%
15/41 • 8 weeks
Psychiatric disorders
mood lability
7.5%
3/40 • 8 weeks
4.9%
2/41 • 8 weeks
Psychiatric disorders
sadness, depression
22.5%
9/40 • 8 weeks
24.4%
10/41 • 8 weeks
Nervous system disorders
memory disturbance
7.5%
3/40 • 8 weeks
2.4%
1/41 • 8 weeks
General disorders
fever
5.0%
2/40 • 8 weeks
4.9%
2/41 • 8 weeks
General disorders
hair loss
5.0%
2/40 • 8 weeks
0.00%
0/41 • 8 weeks

Additional Information

John V. Campo

The Ohio State University

Phone: 614-581-5984

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place