CD: Gastrointestinal Outcomes (2006)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:
To study the mouth-to-cecum transit of a caloric liquid meal in a homogeneous group of symptomatic celiac patients before and after a gluten-free diet, as well as correlate the orocecal transit time with the D-xylose test as an index of proximal malabsorption and severity of the disease.  
Inclusion Criteria:
Homogeneous group of celiac patients presenting with clinical and biochemical evidence of malabsorption and complaining of diarrhea, weight loss and weakness.
Exclusion Criteria:
Pancreatic disease was excluded by normal pancreatic imaging on abdominal ultrasound scans, absence of pancreatic calcifications on plain abdominal x-ray films and normal pancreolauryl test.
Description of Study Protocol:

Recruitment

Methods not defined.  Controls were volunteers from hospital staff.

Design

Case-Control Study.

Blinding used (if applicable)

Not used - lab tests.

Intervention (if applicable)

Gluten-free diet for 6 - 8 months.

Statistical Analysis

Mouth-to-cecum transit time in patients and controls was compared by Student's t test for paired and unpaired data.  Pearson's coefficient r was calculated for each celiac patient between mouth-to-cecum transit time and urinary D-xylose testing, before and after gluten-free diet.

Data Collection Summary:

Timing of Measurements

Breath tests and D-xylose tests were carried out basally and after a period of gluten-free diet. 

Dependent Variables

  • Hydrogen breath test through ingestion of 20 g lactulose
  • Urinary D-xylose tests
  • Small intestine bacterial overgrowth tests
  • Mouth-to-cecum transit time

Independent Variables

  • Gluten free diet for 6 - 8 months, not defined.  Compliance monitored through dietitian interview.

Control Variables

 

Description of Actual Data Sample:

Initial N: 16 celiac disease patients (7 men, 9 women), 20 healthy volunteer controls (8 men, 12 women)

Attrition (final N):  16 patients, 20 controls

Age:  Celiac patients mean age 44 years (range 22 - 68), controls mean age 41.5 years (range 20 - 65) 

Ethnicity:  Not mentioned

Other relevant demographics:  None of the subjects had taken antibiotics or drugs likely to influence GI motility for at least 1 week prior to study 

Anthropometrics:  Controls were not age or sex matched

Location:   Italy

 

Summary of Results:

Other Findings

At the time of diagnosis, mouth-to-cecum transit time was significantly prolonged in celiacs with respect to controls (243 +/- 10 vs 117 +/- 6 minutes, P = 0.0001).

The D-xylose test was also abnormal (average urinary concentration 2.8 +/- 0.25 g, normal values > 4.5) in all celiac patients.

No correlation was found in patients between mouth-to-cecum transit time and urinary D-xylose output (r = 0.22).

After the gluten-free diet period, mouth-to-cecum transit time in celiacs was significantly reduced compared to prediet transit (134 +/- 8 vs 243 +/- 10 min, P = 0.0001) and did not show statistical difference when compared to that found in controls (P = 0.1).

The D-xylose test reverted to normal in all but 2 subjects, who were found to be noncompliant with diet.  

No correlation was found in treated patients between mouth-to-cecum transit time and urinary D-xylose (r = 0.69).

Author Conclusion:
In conclusion, mouth-to-cecum transit time is significantly prolonged in patients affected by untreated celiac disease when compared to healthy controls.  This alteration might not be correlated to intestinal malabsorption, and the prolonged orocecal transit could be due to impaired small bowel function (deranged motility?).  After an adequate gluten-free diet,  intestinal transit returned to normal values, suggesting a link with severe active mucosal lesions.  These data may be of clinical relevance in subgroups of celiacs presenting with symptoms suggestive of small bowel motor dysfunction.
Funding Source:
University/Hospital: Universita degli Studi di Verona; Universita degli Studi di Perugia (Italy); University of North Carolina Center for Functional Gastrointestinal Diseases; University of North Carolina at Chapel Hill
Reviewer Comments:
Recruitment methods not defined.  Small sample size, controls not matched.  Gluten-free diet not defined.
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) Yes
  2. Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about? Yes
  3. Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice? Yes
  4. Is the intervention or procedure feasible? (NA for some epidemiological studies) Yes
 
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? ???
  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? Yes
  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? ???
3. Were study groups comparable? ???
  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? ???
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) Yes
  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.) ???
  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? Yes
  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? Yes
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? Yes
  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? Yes
  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? Yes
  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? Yes
  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? Yes
  7.6. Were other factors accounted for (measured) that could affect outcomes? Yes
  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)? N/A
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? Yes
  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? N/A
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? Yes