EAL

DF: Gastrointestinal Disease (2008)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To examine the optimum dose of ispaghula husk in patients with irritable bowel syndrome (IBS)
To assess the correlation, if any between the relief in patients' symptoms and the whole-gut transit time and the increase in stool weight.

Inclusion Criteria:

Part One Study: 14 consecutive male patients with clinical IBS diagnosis were included
Part Two Study: After completion of Part One study, 19 consecutive male patients with clinical IBS diagnosis were included.

Exclusion Criteria:

Any patient failing to report on the appointed day was excluded from the study.

Description of Study Protocol:

Recruitment

Consecutive male patients.

Design

Two-part study: Part Two was designed after Part One had been completed and the results were available.

Part One was a before-and-after trial: Ispaghula husk was administered in gradually increasing quantities of 10g, 20g and 30g, with no washout period between the doses
Part Two was a randomized crossover trial (single arm): All patients received the three doses (10g, 20g and 30g) of ispaghula husk, given in random order and in a blind fashion, with a washout period of one week between two doses.

Blinding Used

Part One study: No blinding
Part Two study: The person assessing the clinical status was blinded from the dose of fiber received by patient.

Intervention

Part One Study
- Ispaghula husk (processed flea seed husk): Five grams twice daily (10g per day) for 17 days (14 days of treatment and three days of stool collection)
- The dose of fiber was then increased to 20g per day for the next 17 days, followed by 30g per day for the final 17 days.
Part Two Study
- Three doses (10g, 20g and 30g) of ispaghula husk, given in a random order and in a blind fashion with a washout period of one week between two doses.

Statistical Analysis

Paired T-test
Wilcoxon's signed rank sum test for analyzing the changes in the individual symptom scores with different doses of fiber.

Data Collection Summary:

Timing of Measurements

Clinical assessment was made at the end of each two weeks of study period (i.e., within three days after the 14 days of treatment).

Dependent Variables

Symptom improvement score: Clinical assessment for constipation, diarrhea and abdominal pain. For every 25% subjective improvement in a particular symptom, a score of +1 was given with a maximal attainable score of +4 for any one symptom and a maximal attainable score of +12 for the three symptoms. Similarly, for every 25% subjective worsening, a score of -1 was given to a particular symptom. Thus, all patients started with an initial score of 0. Other symptoms were recorded but did not include in the calculation of the symptom improvement score.
Transit time: Whole-gut transit time was measured by the method of Hinton et al
Stool weight: The mean daily stool weight was calculated from the total stool passed during 72 hours, starting immediately after ingestion of the radio-opaque markers.

[Note: Transit time and stool weight were not carried out in the Part Two study.]

Independent Variables

Different doses of ispaghula husk treatment (10g, 20g and 30g).

Control Variables

None.

Description of Actual Data Sample:

Part One Study

Initial N: 14 (100% males)
Attrition (final N): 10
Age: 32.6 (range 21 to 50) years
Ethnicity: No data
Other relevant demographics: The duration of illness before entry into the trial varied from six months to 12 years (mean 3.7 years)
Anthropometrics: No data
Location: India.

Part Two Study

Initial N: 19 (100% males)
Attrition (final N): 10
Age: 26.7±4.7 years
Ethnicity: No data
Other relevant demographics: The duration of illness before entry into the trial ranged from two to 12 years (mean, 4.32 years)
Anthropometrics: No data
Location: India.

Summary of Results:

Part One Study

Doses gradually increased with no washout.

Outcomes of the 10 IBS Patients who Completed the Study

	Baseline (Mean±SD)	10g per Day Fiber (Mean±SD)	20g per Day Fiber (Mean±SD)	30g per Day Fiber (Mean±SD)
Symptom Improvement Score	N/A	4.5±2.8*	8.9±3.1*	9.45±2.1
Stool Weight (grams)	283.5±134	412.7±117.4*	469.3±147.7	509.0±137.6*
Transit Time (hours) [Range]	27.8±10.98 [19-45.5]	28.33±9.7 [21-44.5]	28.12±9.37 [21-43.5]	28.31±9.79 [20.2-43.0]

*P<0.05, significantly different, compared to the previous treatment period of ispaghula husk.

Other Results

There was a correlation between the increase in stool weight and the improvement in the symptom score, with the 10-gram dose of fiber (R=0.64, P<0.05), however no such correlation was noted with the 20-gram (R=0.56) and 30-gram (R=0.09) doses.

Part Two Study

Randomized crossover trial with washout.

Outcomes of the 10 IBS Patients who Completed the Study

	Baseline (Mean±SD)	10g per Day Fiber (Mean±SD)	20g per Day Fiber (Mean±SD)	30g per Day Fiber (Mean±SD)
Symptom Improvement Score	N/A	4.8±4.4*	7.15±3.72*	6.4±4.25

*P<0.01, significantly different, compared to the previous treatment period of ispaghula husk.

Dropouts in Part One and Part Two Studies

13 (39%) out of 33 patients dropped out. Most of these patients (N=8; 61.5%) dropped out while on the 30-gram dose because they found it difficult to consume such large quantities of fiber. The remaining five (two on 10-gram and three on 20-gram dose) dropped out because they felt sufficiently well and did not wish to carry on with the study.

Author Conclusion:

The two higher doses were equally effective and both were significantly superior to the 10-gram dose. Patient compliance was reduced only with the 30-gram dose of ispaghula. We recommend, therefore, that 20g is the optimal dose of ispaghula husk in the treatment of IBS, at least in Indian patients.
The mechanism by which dietary fiber improves the patients symptoms is related to some extent to the increase in the stool weight, but is independent of the whole-gut transit time of food.

Funding Source:

University/Hospital:

GB Pant Hospital (New Dehli India

Reviewer Comments:

Major limitation: Small sample size and high dropout rate. Only completers were analyzed.
Placebo effect is likely for symptom improvement outcomes in Study One, but it is less likely in view of the results obtained in Part Two of the study because of the randomization of treatments
The authors failed to adjust for multiple testing in their statistical analyses, but judging from some of the highly significant P-values, the significance would likely remain after adjusting for multiple testing.

Quality Criteria Checklist: Primary Research
Relevance Questions
	1.	Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies)	N/A
	2.	Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about?	N/A
	3.	Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice?	N/A
	4.	Is the intervention or procedure feasible? (NA for some epidemiological studies)	N/A

Validity Questions
1.	Was the research question clearly stated?		Yes
	1.1.	Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?	Yes
	1.2.	Was (were) the outcome(s) [dependent variable(s)] clearly indicated?	Yes
	1.3.	Were the target population and setting specified?	Yes
2.	Was the selection of study subjects/patients free from bias?		Yes
	2.1.	Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study?	Yes
	2.2.	Were criteria applied equally to all study groups?	N/A
	2.3.	Were health, demographics, and other characteristics of subjects described?	Yes
	2.4.	Were the subjects/patients a representative sample of the relevant population?	No
3.	Were study groups comparable?		No
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	Yes
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	No
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	No
	3.4.	If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis?	N/A
	3.5.	If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.)	N/A
	3.6.	If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")?	N/A
4.	Was method of handling withdrawals described?		Yes
	4.1.	Were follow-up methods described and the same for all groups?	Yes
	4.2.	Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.)	Yes
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	No
	4.4.	Were reasons for withdrawals similar across groups?	N/A
	4.5.	If diagnostic test, was decision to perform reference test not dependent on results of test under study?	N/A
5.	Was blinding used to prevent introduction of bias?		No
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	No
	5.2.	Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.)	Yes
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	N/A
	5.4.	In case control study, was case definition explicit and case ascertainment not influenced by exposure status?	N/A
	5.5.	In diagnostic study, were test results blinded to patient history and other test results?	N/A
6.	Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described?		Yes
	6.1.	In RCT or other intervention trial, were protocols described for all regimens studied?	Yes
	6.2.	In observational study, were interventions, study settings, and clinicians/provider described?	N/A
	6.3.	Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?	Yes
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	Yes
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	No
	6.6.	Were extra or unplanned treatments described?	N/A
	6.7.	Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?	N/A
	6.8.	In diagnostic study, were details of test administration and replication sufficient?	N/A
7.	Were outcomes clearly defined and the measurements valid and reliable?		Yes
	7.1.	Were primary and secondary endpoints described and relevant to the question?	Yes
	7.2.	Were nutrition measures appropriate to question and outcomes of concern?	Yes
	7.3.	Was the period of follow-up long enough for important outcome(s) to occur?	Yes
	7.4.	Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures?	Yes
	7.5.	Was the measurement of effect at an appropriate level of precision?	???
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	No
	7.7.	Were the measurements conducted consistently across groups?	Yes
8.	Was the statistical analysis appropriate for the study design and type of outcome indicators?		Yes
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	Yes
	8.2.	Were correct statistical tests used and assumptions of test not violated?	Yes
	8.3.	Were statistics reported with levels of significance and/or confidence intervals?	Yes
	8.4.	Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)?	No
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	No
	8.6.	Was clinical significance as well as statistical significance reported?	Yes
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	No
9.	Are conclusions supported by results with biases and limitations taken into consideration?		Yes
	9.1.	Is there a discussion of findings?	Yes
	9.2.	Are biases and study limitations identified and discussed?	Yes
10.	Is bias due to study's funding or sponsorship unlikely?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	???