Fabry's Disease
Conditions
Keywords
Fabry's Disease, Fabry
Brief summary
Patients will undergo a SmartPill test to gain additional understanding of Fabry disease manifestation via motility abnormalities in order to improve symptom targeted therapy. An additional Endoscopic mucosal resection may be performed on further qualifying patients. Tissue analysis from this biopsy will include evaluation of abnormalities of cellular structure and morphology with correlation with gastrointestinal complaints for each patient and comparison against age matched non-Fabry patient tissue. The hypothesis is that patients with fabry disease will have abnormal motility which will correlate with the patients symptoms and quality of life as noted on the questionnaires.
Detailed description
Background: Gastrointestinal manifestations such as abdominal pain, diarrhea and nausea are prominent and, although typically non life-threatening, can frequently cause significant morbidity and burden in a patient with Fabry disease. Additional in depth understanding of gastrointestinal symptoms pathophysiology in Fabry disease is acutely needed in order to develop more specific evaluation of the symptoms and advance the treatment of these patients. Hypothesis: Patients with gastrointestinal (GI) symptoms will have delayed motility on the SmartPill study, abnormal histologic findings on mucosal resection and symptoms that correlate with abnormal histologic and SmartPill findings. By gaining additional insight into the characterization of symptoms and the relationship to dysmotility, we anticipate improved and more focused adjunct therapies for the patients. Methods: This study will consist of a screening visit, a SmartPill testing procedure visit, and a follow up visit for all subjects enrolled in the study. Fifteen of these patients, who clinically warranted sigmoidoscopy, will be asked to also complete an endoscopic mucosal resection (EMR) visit in addition to the other aspects of the study. Thus, each subject will report to the study site for at least 3 visits and up to 4 visits.
Interventions
DEVICESmartpill
The SmartPill Test is approved by the U.S. Food and Drug Administration (FDA) to measure transit time in the GI tract. This procedure uses the SmartPill capsule, a receiver, and computer software.
PROCEDUREEndoscopic Mucosal Resection
a Sigmoidoscopy is an exam used to evaluate the lower part of the large intestine) during which an Endoscopic Mucosal Resection (removal of a small amount of tissue from the outermost layer of gut wall) will be completed.
Sponsors
Massachusetts General Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Adults ages 18-70 years who have diagnosed Fabry disease either by enzyme testing in males or by enzyme and/or genetically confirmed mutation in females. * Adults with Fabry disease having any gastrointestinal complaints within the past year. * Endoscopic Mucosal Resection ONLY - Symptomatic subjects necessitating a sigmoidoscopy who are enzyme replacement therapy (ERT) naive OR less than 6 months of treatment.
Exclusion criteria
1. Fabry disease with other concomitant gastrointestinal diagnosis (Example: Inflammatory Bowel Disease, Celiac Disease) 2. Pregnancy 3. Endoscopic mucosal resection exclusions: 1. Any contraindication to conscious sedation, 2. Contraindication to endoscopy, 3. Untreated or unmanageable coagulopathy, 4. Thrombocytopenia (\<50). 5. Patient on ERT for more than 6 months. 4. Exclusions for SmartPill: 1. Previous history of bezoars. 2. Prior GI surgery except for cholecystectomy, appendectomy, or Nissen fundoplication. 3. Any abdominal surgery within the past 3 months 4. History of diverticulitis, diverticular stricture, and other intestinal strictures 5. Tobacco use within eight hours prior to capsule ingestion and during the initial 8-hour recording on Day 0 or the Ingestion visit. 6. Alcohol use within eight hours prior to capsule ingestion and throughout the entire monitoring period (5 days). 7. BMI \> 38 8. Allergies to components of the SmartBar 9. Use of medical devices such as pacemakers, infusion pumps, or insulin pumps. 10. Uncontrolled diabetes with a hemoglobin A1C greater than 10.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Gastric Emptying Transit Time Measured Via SmartPill Study | Up to 5 hours | The primary outcome of dysmotility will be the measurement of gastric emptying transit time via a SmartPill study. Delayed GET are defined as longer than 5 hours. |
| Small Bowel Transit Time Measured Via SmartPill Study | Up to 6 hours | The primary outcome of dysmotility will be the measurement of small bowel transit time via a SmartPill study. Delayed SBTT are defined as longer than 6 hours. |
| Colonic Transit Time Measured Via SmartPill Study | Up to 67 hours | The primary outcome of dysmotility will be the measurement of colonic transit time via a SmartPill study. Delayed CTT is defined as longer than 59 hours. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Delayed Small Bowel Transit Measured Via SmartPill Study | Up to 6 hours | The secondary outcome of dysmotility will be the measurement of delayed bowel transit time via a SmartPill study. Delayed SBTT are defined as longer than 6 hours. |
| Delayed Colonic Transit Measured Via SmartPill Study | Up to 67 hours | The secondary outcome of dysmotility will be the measurement of delayed colonic transit time via a SmartPill study. Delayed CTT is defined as longer than 59 hours. |
| Symptom Severity Index | At 67 hours, data reported over the last 4 weeks | Patient reported severity of certain symptoms over the last 4 weeks on a scale of 0 to 10 (bloating, abdominal discomfort, incomplete evacuation, straining and urgency). Higher score would mean worse (more symptoms) outcome. |
| Symptom Frequency Assessment (SFA) | At 67 hours, data reported over the last 7 days | Patients reported the number of complete BMs they had during the last week (minimum could be 0 and the maximum could be any number greater than 0). Higher/lower scores could be the better or worse outcome (e.g., 0 bowel movements all week would be a worse outcome but over 10 bowel movements would be worse as well), it just depends on the extent. |
| Gastrointestinal Symptom Assessment and Quality of Life, Work, and Productivity Via Questionnaires | Up to 4 weeks | Participants will complete several questionnaires during study participation regarding gastrointestinal symptoms (lower and upper GI). These results will be used to determine overall gastrointestinal involvement and will be correlated with transit time and histologic findings |
| Beck's Depression Inventory (BDI) | At 4 weeks | Beck's Depression Inventory (BDI): is a 21-item tool assessing the existence and severity of symptoms of depression, as defined by the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV; 1994). The items correspond to symptoms of depression and are a four-point scale for each item ranging from 0 to 3. They are summed to give a single BDI score between 0-63 (where higher results reflect more severe depression). Grades are 1-10: normal, 11-16: mild mood disturbance, 17-20: borderline clinical depression, 21-30: moderate depression, 31-40: severe depression, and \>40 extreme depression 6. Moderate-severe depression was defined as a score of 21 and above. |
| Work Productivity and Activity Impairment (WPAI) | At 7 days | Work Productivity and Activity Impairment (WPAI): examines the effect of GI symptoms on loss of work time and loss of productivity. Patients indicated if they are unemployed. For employed patients, scores are presented as percentage of time lost during the last week (hours lost due to GI symptoms out of the hours that patient should have worked, excluding the time lost on participating in the study). Higher percentages indicate greater impairment. Work missed percentage, reduced productivity percentage, and work-productivity impairment percentage (combining the 2 scores) are calculated 7. We defined work/productivity impairment as either being unemployed or having lost 40% or more of work time or productivity. For employed patients, scores are presented as percentage of time lost during the last week (hours lost due to GI symptoms out of the hours that patient should have worked, excluding the time lost on participating in the study). |
| IBS Quality of Life (IBS QoL) and Sub-scores | At 4 weeks | Irritable bowel syndrome quality of life (IBS-QOL): Assesses bowel specific QOL. It consists of 34 items of a 5-point Likert scale. The total score is summed and then transformed to a 0-100 scale, where 0 is low QoL, and 100 is the best QoL. Different IBS-QOL items can also be categorized to eight subscale scores (Dysphoria, Interference with Activity, Body Image, Health Worry, Food Avoidance, Social Reaction, Sexual, Relationships). Note be made, that the IBS-QOL examines the effect of bowel problems on different aspect of QOL, and so was used to assess the effect of gut symptoms on the patients' QOL. Higher scores are better outcome. |
| Bristol Stool Scale | At 7 days | Bristol Stool Scale: patients indicate their last 7 days stool consistency on 1-7 visual scale. The Bristol stool scale correlates with colonic transit time. Higher scores do not indicate better or worse outcomes. It is a visual scale. |
| Hamilton Anxiety Rating Scale (HAM-A) | At 4 weeks | The scale consists of 14 items, each defined by a series of symptoms, and measures both psychic anxiety (mental agitation and psychological distress) and somatic anxiety (physical complaints related to anxiety). Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where \<7 indicates no or minimal severity, 8-14 is mild anxiety, 15-23 is moderate anxiety and 24 and worse is severe anxiety 5. Moderate-severe anxiety was defined as a score of 15 and above. |
| Age of Symptom Start | Up to 4 weeks | — |
| Delayed Gastric Emptying Measured Via SmartPill Study | Up to 5 hours | The secondary outcome of dysmotility will be the measurement of delayed gastric emptying measured via a SmartPill study. Delayed GET are defined as longer than 5 hours. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Female Demographics | 28 |
| Male Demographics | 20 |
| Total | 48 |
Baseline characteristics
| Characteristic | Male | Female | Total |
|---|---|---|---|
| Age, Continuous | 46.5 years | 46 years | 46.5 years |
| Any neurologic involvement | 19 Participants | 27 Participants | 46 Participants |
| Asthma systemic involvement | 5 Participants | 8 Participants | 13 Participants |
| Cardiac system involvement | 17 Participants | 20 Participants | 37 Participants |
| Central nervous system (serious) involvement - make clear this excludes CN | 3 Participants | 7 Participants | 10 Participants |
| Dermatology systemic involvement | 13 Participants | 8 Participants | 21 Participants |
| Enzyme replacement therapy > 6 months | 13 Participants | 15 Participants | 28 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 1 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 17 Participants | 26 Participants | 43 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Ophthalmic systemic involvement | 9 Participants | 22 Participants | 31 Participants |
| Peripheral nervous system involvement | 19 Participants | 27 Participants | 46 Participants |
| Presenting age of any neurologic systemic involvement | 10 years | 7 years | 9 years |
| Presenting age of cardiac systemic involvement | 32 years | 34 years | 32.5 years |
| Presenting age of ophthalmic systemic involvement | 31 years | 15.5 years | 24.5 years |
| Presenting age of psychiatric systemic involvement | 36.5 years | 33.5 years | 34.5 years |
| Presenting age of renal systemic involvement | 32 years | 20.5 years | 28 years |
| Presenting age of respiratory (asthma) systemic involvement | 9 years | 20 years | 19 years |
| Psychiatric systemic involvement | 6 Participants | 20 Participants | 26 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) White | 16 Participants | 27 Participants | 43 Participants |
| Region of Enrollment United States | 20 Participants | 28 Participants | 48 Participants |
| Renal systemic involvement | 13 Participants | 8 Participants | 21 Participants |
| Sex: Female, Male Female | 0 Participants | 28 Participants | 28 Participants |
| Sex: Female, Male Male | 20 Participants | 0 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 48 | 0 / 13 |
| other Total, other adverse events | 1 / 48 | 1 / 13 |
| serious Total, serious adverse events | 0 / 48 | 0 / 13 |
Outcome results
Primary
Colonic Transit Time Measured Via SmartPill Study
The primary outcome of dysmotility will be the measurement of colonic transit time via a SmartPill study. Delayed CTT is defined as longer than 59 hours.
Time frame: Up to 67 hours
Population: Demographics
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Female | Colonic Transit Time Measured Via SmartPill Study | 38.1 Hours |
| Male | Colonic Transit Time Measured Via SmartPill Study | 21.3 Hours |
Primary
Gastric Emptying Transit Time Measured Via SmartPill Study
The primary outcome of dysmotility will be the measurement of gastric emptying transit time via a SmartPill study. Delayed GET are defined as longer than 5 hours.
Time frame: Up to 5 hours
Population: Demographics
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Female | Gastric Emptying Transit Time Measured Via SmartPill Study | 2.9 Hours |
| Male | Gastric Emptying Transit Time Measured Via SmartPill Study | 2.8 Hours |
Primary
Small Bowel Transit Time Measured Via SmartPill Study
The primary outcome of dysmotility will be the measurement of small bowel transit time via a SmartPill study. Delayed SBTT are defined as longer than 6 hours.
Time frame: Up to 6 hours
Population: Demographics
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Female | Small Bowel Transit Time Measured Via SmartPill Study | 4.3 Hours |
| Male | Small Bowel Transit Time Measured Via SmartPill Study | 4.5 Hours |
Secondary
Age of Symptom Start
Time frame: Up to 4 weeks
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Female | Age of Symptom Start | Age of first gastrointestinal symptoms | 15 years |
| Female | Age of Symptom Start | Age of abdominal pain symptom start | 25 years |
| Female | Age of Symptom Start | Age of Diarrhea symptom start | 16 years |
| Female | Age of Symptom Start | Age of constipation symptom start | 15 years |
| Female | Age of Symptom Start | Age of nausea symptom start | 28 years |
| Female | Age of Symptom Start | Age of vomiting symptom start | 13 years |
| Male | Age of Symptom Start | Age of nausea symptom start | 20 years |
| Male | Age of Symptom Start | Age of first gastrointestinal symptoms | 10 years |
| Male | Age of Symptom Start | Age of constipation symptom start | 15 years |
| Male | Age of Symptom Start | Age of abdominal pain symptom start | 10 years |
| Male | Age of Symptom Start | Age of vomiting symptom start | 20 years |
| Male | Age of Symptom Start | Age of Diarrhea symptom start | 10 years |
Secondary
Beck's Depression Inventory (BDI)
Beck's Depression Inventory (BDI): is a 21-item tool assessing the existence and severity of symptoms of depression, as defined by the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV; 1994). The items correspond to symptoms of depression and are a four-point scale for each item ranging from 0 to 3. They are summed to give a single BDI score between 0-63 (where higher results reflect more severe depression). Grades are 1-10: normal, 11-16: mild mood disturbance, 17-20: borderline clinical depression, 21-30: moderate depression, 31-40: severe depression, and \>40 extreme depression 6. Moderate-severe depression was defined as a score of 21 and above.
Time frame: At 4 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Female | Beck's Depression Inventory (BDI) | 10.5 score on a scale |
| Male | Beck's Depression Inventory (BDI) | 6.5 score on a scale |
Secondary
Bristol Stool Scale
Bristol Stool Scale: patients indicate their last 7 days stool consistency on 1-7 visual scale. The Bristol stool scale correlates with colonic transit time. Higher scores do not indicate better or worse outcomes. It is a visual scale.
Time frame: At 7 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Female | Bristol Stool Scale | 4 score on a scale |
| Male | Bristol Stool Scale | 6 score on a scale |
Secondary
Delayed Colonic Transit Measured Via SmartPill Study
The secondary outcome of dysmotility will be the measurement of delayed colonic transit time via a SmartPill study. Delayed CTT is defined as longer than 59 hours.
Time frame: Up to 67 hours
Population: Demographics
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Female | Delayed Colonic Transit Measured Via SmartPill Study | 8 Participants |
| Male | Delayed Colonic Transit Measured Via SmartPill Study | 2 Participants |
Secondary
Delayed Gastric Emptying Measured Via SmartPill Study
The secondary outcome of dysmotility will be the measurement of delayed gastric emptying measured via a SmartPill study. Delayed GET are defined as longer than 5 hours.
Time frame: Up to 5 hours
Population: Demographics
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Female | Delayed Gastric Emptying Measured Via SmartPill Study | 3 Participants |
| Male | Delayed Gastric Emptying Measured Via SmartPill Study | 2 Participants |
Secondary
Delayed Small Bowel Transit Measured Via SmartPill Study
The secondary outcome of dysmotility will be the measurement of delayed bowel transit time via a SmartPill study. Delayed SBTT are defined as longer than 6 hours.
Time frame: Up to 6 hours
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Female | Delayed Small Bowel Transit Measured Via SmartPill Study | 1 Participants |
| Male | Delayed Small Bowel Transit Measured Via SmartPill Study | 2 Participants |
Secondary
Gastrointestinal Symptom Assessment and Quality of Life, Work, and Productivity Via Questionnaires
Participants will complete several questionnaires during study participation regarding gastrointestinal symptoms (lower and upper GI). These results will be used to determine overall gastrointestinal involvement and will be correlated with transit time and histologic findings
Time frame: Up to 4 weeks
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Female | Gastrointestinal Symptom Assessment and Quality of Life, Work, and Productivity Via Questionnaires | Dysregulated bowel habits | 25 Participants |
| Female | Gastrointestinal Symptom Assessment and Quality of Life, Work, and Productivity Via Questionnaires | Reporting chronic diarrhea | 14 Participants |
| Female | Gastrointestinal Symptom Assessment and Quality of Life, Work, and Productivity Via Questionnaires | Reporting chronic constipation | 20 Participants |
| Female | Gastrointestinal Symptom Assessment and Quality of Life, Work, and Productivity Via Questionnaires | Reporting only diarrhea | 5 Participants |
| Female | Gastrointestinal Symptom Assessment and Quality of Life, Work, and Productivity Via Questionnaires | Reporting only constipation | 11 Participants |
| Female | Gastrointestinal Symptom Assessment and Quality of Life, Work, and Productivity Via Questionnaires | Chronic abdominal pain | 25 Participants |
| Female | Gastrointestinal Symptom Assessment and Quality of Life, Work, and Productivity Via Questionnaires | Symptoms compatible with IBS | 23 Participants |
| Female | Gastrointestinal Symptom Assessment and Quality of Life, Work, and Productivity Via Questionnaires | Bloating | 23 Participants |
| Female | Gastrointestinal Symptom Assessment and Quality of Life, Work, and Productivity Via Questionnaires | Functional dyspepsia | 26 Participants |
| Female | Gastrointestinal Symptom Assessment and Quality of Life, Work, and Productivity Via Questionnaires | Dysphagia | 2 Participants |
| Female | Gastrointestinal Symptom Assessment and Quality of Life, Work, and Productivity Via Questionnaires | nausea and vomiting | 15 Participants |
| Female | Gastrointestinal Symptom Assessment and Quality of Life, Work, and Productivity Via Questionnaires | Gastroesophageal reflux disease symptoms | 15 Participants |
| Female | Gastrointestinal Symptom Assessment and Quality of Life, Work, and Productivity Via Questionnaires | Moderate severe depression | 4 Participants |
| Female | Gastrointestinal Symptom Assessment and Quality of Life, Work, and Productivity Via Questionnaires | Moderate severe anxiety | 18 Participants |
| Female | Gastrointestinal Symptom Assessment and Quality of Life, Work, and Productivity Via Questionnaires | Unemployed by Work Productivity and Activity Impairment | 5 Participants |
| Female | Gastrointestinal Symptom Assessment and Quality of Life, Work, and Productivity Via Questionnaires | Work loss- 40% and more by Work Productivity and Activity Impairment | 2 Participants |
| Female | Gastrointestinal Symptom Assessment and Quality of Life, Work, and Productivity Via Questionnaires | Reduced productivity 40% and more by Work Productivity and Activity Impairment | 9 Participants |
| Female | Gastrointestinal Symptom Assessment and Quality of Life, Work, and Productivity Via Questionnaires | Work/productivity impairment by Work Productivity and Activity Impairment | 14 Participants |
| Male | Gastrointestinal Symptom Assessment and Quality of Life, Work, and Productivity Via Questionnaires | Moderate severe anxiety | 13 Participants |
| Male | Gastrointestinal Symptom Assessment and Quality of Life, Work, and Productivity Via Questionnaires | Dysregulated bowel habits | 17 Participants |
| Male | Gastrointestinal Symptom Assessment and Quality of Life, Work, and Productivity Via Questionnaires | Dysphagia | 0 Participants |
| Male | Gastrointestinal Symptom Assessment and Quality of Life, Work, and Productivity Via Questionnaires | Reporting chronic diarrhea | 16 Participants |
| Male | Gastrointestinal Symptom Assessment and Quality of Life, Work, and Productivity Via Questionnaires | Work/productivity impairment by Work Productivity and Activity Impairment | 13 Participants |
| Male | Gastrointestinal Symptom Assessment and Quality of Life, Work, and Productivity Via Questionnaires | Reporting chronic constipation | 11 Participants |
| Male | Gastrointestinal Symptom Assessment and Quality of Life, Work, and Productivity Via Questionnaires | nausea and vomiting | 7 Participants |
| Male | Gastrointestinal Symptom Assessment and Quality of Life, Work, and Productivity Via Questionnaires | Reporting only diarrhea | 6 Participants |
| Male | Gastrointestinal Symptom Assessment and Quality of Life, Work, and Productivity Via Questionnaires | Unemployed by Work Productivity and Activity Impairment | 9 Participants |
| Male | Gastrointestinal Symptom Assessment and Quality of Life, Work, and Productivity Via Questionnaires | Reporting only constipation | 1 Participants |
| Male | Gastrointestinal Symptom Assessment and Quality of Life, Work, and Productivity Via Questionnaires | Gastroesophageal reflux disease symptoms | 2 Participants |
| Male | Gastrointestinal Symptom Assessment and Quality of Life, Work, and Productivity Via Questionnaires | Chronic abdominal pain | 14 Participants |
| Male | Gastrointestinal Symptom Assessment and Quality of Life, Work, and Productivity Via Questionnaires | Reduced productivity 40% and more by Work Productivity and Activity Impairment | 3 Participants |
| Male | Gastrointestinal Symptom Assessment and Quality of Life, Work, and Productivity Via Questionnaires | Symptoms compatible with IBS | 14 Participants |
| Male | Gastrointestinal Symptom Assessment and Quality of Life, Work, and Productivity Via Questionnaires | Moderate severe depression | 0 Participants |
| Male | Gastrointestinal Symptom Assessment and Quality of Life, Work, and Productivity Via Questionnaires | Bloating | 10 Participants |
| Male | Gastrointestinal Symptom Assessment and Quality of Life, Work, and Productivity Via Questionnaires | Work loss- 40% and more by Work Productivity and Activity Impairment | 2 Participants |
| Male | Gastrointestinal Symptom Assessment and Quality of Life, Work, and Productivity Via Questionnaires | Functional dyspepsia | 13 Participants |
Secondary
Hamilton Anxiety Rating Scale (HAM-A)
The scale consists of 14 items, each defined by a series of symptoms, and measures both psychic anxiety (mental agitation and psychological distress) and somatic anxiety (physical complaints related to anxiety). Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where \<7 indicates no or minimal severity, 8-14 is mild anxiety, 15-23 is moderate anxiety and 24 and worse is severe anxiety 5. Moderate-severe anxiety was defined as a score of 15 and above.
Time frame: At 4 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Female | Hamilton Anxiety Rating Scale (HAM-A) | 16.5 score on a scale |
| Male | Hamilton Anxiety Rating Scale (HAM-A) | 16.5 score on a scale |
Secondary
IBS Quality of Life (IBS QoL) and Sub-scores
Irritable bowel syndrome quality of life (IBS-QOL): Assesses bowel specific QOL. It consists of 34 items of a 5-point Likert scale. The total score is summed and then transformed to a 0-100 scale, where 0 is low QoL, and 100 is the best QoL. Different IBS-QOL items can also be categorized to eight subscale scores (Dysphoria, Interference with Activity, Body Image, Health Worry, Food Avoidance, Social Reaction, Sexual, Relationships). Note be made, that the IBS-QOL examines the effect of bowel problems on different aspect of QOL, and so was used to assess the effect of gut symptoms on the patients' QOL. Higher scores are better outcome.
Time frame: At 4 weeks
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Female | IBS Quality of Life (IBS QoL) and Sub-scores | Interference with Activity sub-score | 57.1 score on a scale |
| Female | IBS Quality of Life (IBS QoL) and Sub-scores | Social reaction sub-score | 87.5 score on a scale |
| Female | IBS Quality of Life (IBS QoL) and Sub-scores | Health Worry sub-score | 75 score on a scale |
| Female | IBS Quality of Life (IBS QoL) and Sub-scores | Sexual sub-score | 100 score on a scale |
| Female | IBS Quality of Life (IBS QoL) and Sub-scores | Body Image sub-score | 68.8 score on a scale |
| Female | IBS Quality of Life (IBS QoL) and Sub-scores | Relationships sub-score | 100 score on a scale |
| Female | IBS Quality of Life (IBS QoL) and Sub-scores | Food avoidance sub-score | 50 score on a scale |
| Female | IBS Quality of Life (IBS QoL) and Sub-scores | IBS-QOL | 80.2 score on a scale |
| Female | IBS Quality of Life (IBS QoL) and Sub-scores | Dysphoria sub-score | 85.7 score on a scale |
| Male | IBS Quality of Life (IBS QoL) and Sub-scores | IBS-QOL | 81.6 score on a scale |
| Male | IBS Quality of Life (IBS QoL) and Sub-scores | Dysphoria sub-score | 85.7 score on a scale |
| Male | IBS Quality of Life (IBS QoL) and Sub-scores | Interference with Activity sub-score | 46.4 score on a scale |
| Male | IBS Quality of Life (IBS QoL) and Sub-scores | Body Image sub-score | 87.5 score on a scale |
| Male | IBS Quality of Life (IBS QoL) and Sub-scores | Health Worry sub-score | 83.3 score on a scale |
| Male | IBS Quality of Life (IBS QoL) and Sub-scores | Food avoidance sub-score | 75 score on a scale |
| Male | IBS Quality of Life (IBS QoL) and Sub-scores | Social reaction sub-score | 84.4 score on a scale |
| Male | IBS Quality of Life (IBS QoL) and Sub-scores | Sexual sub-score | 100 score on a scale |
| Male | IBS Quality of Life (IBS QoL) and Sub-scores | Relationships sub-score | 91.7 score on a scale |
Secondary
Symptom Frequency Assessment (SFA)
Patients reported the number of complete BMs they had during the last week (minimum could be 0 and the maximum could be any number greater than 0). Higher/lower scores could be the better or worse outcome (e.g., 0 bowel movements all week would be a worse outcome but over 10 bowel movements would be worse as well), it just depends on the extent.
Time frame: At 67 hours, data reported over the last 7 days
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Female | Symptom Frequency Assessment (SFA) | Daily bowel movements | 1 units on a scale |
| Female | Symptom Frequency Assessment (SFA) | Weekly bowel movements | 5.5 units on a scale |
| Male | Symptom Frequency Assessment (SFA) | Daily bowel movements | 2.5 units on a scale |
| Male | Symptom Frequency Assessment (SFA) | Weekly bowel movements | 16 units on a scale |
Secondary
Symptom Severity Index
Patient reported severity of certain symptoms over the last 4 weeks on a scale of 0 to 10 (bloating, abdominal discomfort, incomplete evacuation, straining and urgency). Higher score would mean worse (more symptoms) outcome.
Time frame: At 67 hours, data reported over the last 4 weeks
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Female | Symptom Severity Index | Abdominal discomfort | 6.5 score on a scale |
| Female | Symptom Severity Index | Straining while defecating | 3.5 score on a scale |
| Female | Symptom Severity Index | Sense of incomplete evacuation | 3.5 score on a scale |
| Female | Symptom Severity Index | Bowel urgency | 4 score on a scale |
| Female | Symptom Severity Index | Bloating | 6 score on a scale |
| Male | Symptom Severity Index | Bowel urgency | 4 score on a scale |
| Male | Symptom Severity Index | Bloating | 2 score on a scale |
| Male | Symptom Severity Index | Abdominal discomfort | 4 score on a scale |
| Male | Symptom Severity Index | Sense of incomplete evacuation | 2 score on a scale |
| Male | Symptom Severity Index | Straining while defecating | 1.5 score on a scale |
Secondary
Work Productivity and Activity Impairment (WPAI)
Work Productivity and Activity Impairment (WPAI): examines the effect of GI symptoms on loss of work time and loss of productivity. Patients indicated if they are unemployed. For employed patients, scores are presented as percentage of time lost during the last week (hours lost due to GI symptoms out of the hours that patient should have worked, excluding the time lost on participating in the study). Higher percentages indicate greater impairment. Work missed percentage, reduced productivity percentage, and work-productivity impairment percentage (combining the 2 scores) are calculated 7. We defined work/productivity impairment as either being unemployed or having lost 40% or more of work time or productivity. For employed patients, scores are presented as percentage of time lost during the last week (hours lost due to GI symptoms out of the hours that patient should have worked, excluding the time lost on participating in the study).
Time frame: At 7 days
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Female | Work Productivity and Activity Impairment (WPAI) | work missed (%) | 0 percentage of time lost during the last |
| Female | Work Productivity and Activity Impairment (WPAI) | reduced productivity while working (%) | 20 percentage of time lost during the last |
| Female | Work Productivity and Activity Impairment (WPAI) | work productivity impairment (%) | 20 percentage of time lost during the last |
| Male | Work Productivity and Activity Impairment (WPAI) | work missed (%) | 0 percentage of time lost during the last |
| Male | Work Productivity and Activity Impairment (WPAI) | reduced productivity while working (%) | 10 percentage of time lost during the last |
| Male | Work Productivity and Activity Impairment (WPAI) | work productivity impairment (%) | 10 percentage of time lost during the last |