Irritable Bowel Syndrome
Conditions
Brief summary
This study is being done to see if St. John's wort helps people with irritable bowel syndrome, otherwise known as IBS. St. John's wort is a herbal supplement derived from the St. John's wort plant. It has been shown to be helpful in several medical conditions such as depression as well as other pain syndromes.
Detailed description
Eligibility criteria: 1. Established diagnosis of IBS 2. 18-70 years of age 4\) U.S. resident 5) English-speaking (able to provide consent and complete questionnaires) 6) Able to participate in all aspects of the study You will be asked to do the following: * Undergo a screening interview and physical examination * Take a urine pregnancy test (if applicable) * Take a study pill twice daily for 12 weeks(3 months) * Complete daily symptom diaries and bi-weekly questionnaires for 12 weeks. * Complete a questionnaire at 6 months after the active phase of the study is over.
Interventions
DRUGSt. John's wort
Dosage form: Tablet (450 mg) Dose: 450 mg twice a day, placebo twice a day
DRUGPlacebo
Dosage form: Tablet (450 mg) Dose: 450 mg twice a day, placebo twice a day
Sponsors
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Established diagnosis of IBS * Meet Rome II diagnostic criteria for IBS * 18-70 years of age * U.S. resident * English-speaking (able to provide consent and complete questionnaires) * Able to participate in all aspects of the study
Exclusion criteria
* Known alternative/concurrent gastrointestinal diagnosis (e.g. Crohn's disease, ulcerative colitis, microscopic colitis, celiac sprue, chronic pancreatitis or pancreatic insufficiency, scleroderma, chronic intestinal pseudo-obstruction, bacterial overgrowth, recent (\<6 months) intestinal bacterial/protozoal/ parasitic infections, HIV, fecal incontinence, small bowel or colonic resection, pelvic floor dysfunction, paraplegia or quadriplegia) * Current symptoms of severe depression, as measured by Center for Epidemiological Studies Depression Scale (CES-D) score * Mental retardation or any condition requiring a legal guardian * Current or past history of psychotic disorder (schizophrenia, bipolar disorder) * Recent or current use (within past 30 days) of select mood or pain or symptom-altering medications: * benzodiazepine use * substance abuse * narcotic use * antihistamine use * barbiturates * zaleplon (Sonata) * Recent or current use (within past 30 days) of drugs that interact with SJW: * antidepressants or antipsychotics * tramadol (Ultram) * sumatriptan (Imitrex) * digoxin (Lanoxin) * anticonvulsants (e.g. carbamazepine or phenytoin) * immunosuppressants: cyclosporine and tacrolimus * HIV protease inhibitors (e.g. indinavir), non-nucleoside reverse transcriptase inhibitors (e.g. nevirapine) * warfarin (Coumadin) * theophylline * chemotherapy * sulfa-containing drugs * piroxicam (Feldene) * simvastatin (Zocor) * sibutramine (Meridia) * verapamil (Calan or Isoptin) * Planned surgery (especially transplant) or anesthesia exposure during trial * Known photosensitivity or planned photodiagnostic or phototherapy procedures * Are pregnant, lactating, likely to become pregnant during medication phase and not willing to use a reliable form of contraception (barrier contraceptives, diaphragm, injections, intrauterine device, surgical sterilization, and abstinence) * Recent or current use (within 30 days) of SJW, other herbal products for IBS, investigational drug use * Known allergy to SJW * Significant acute or chronic progressive neurologic, hepatic, renal, cardiovascular, respiratory or metabolic disease * Recent history of alcohol or substance dependence use or abuse * Another household member or relative participating in the study * Professional drivers or operators of heavy machinery * Major cardiovascular events in the last 6 months * Use of IBS-specific drugs such as tegaserod (Zelnorm) and Lotronex (Alosetron) (within 30 days)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Bowel Symptom Scores (BSS) | After 12 weeks of treatment | The primary end point was the overall self-reported BSS after 12 weeks of therapy for all randomized participants to assess for differences between treatment groups at the end of the treatment period (12 weeks). The BSS is a 100-mm visual analog scale for the different symptoms of IBS (pain/discomfort, constipation, diarrhea, and overall severity). Symptoms on the BSS can range from 0 = no pain to 100 = extreme pain. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adequate Relief ≤ 50% During the Last 4 Weeks of Therapy | Last 4 weeks of therapy | Participants who reported yes or no to having adequate relief of their IBS symptoms at least 50% during the last 4 weeks of therapy. |
| Irritable Bowel Syndrome - Quality of Life (IBS-QoL) Score | 12 weeks of treatment | The IBS-QOL is a self-report quality-of-life measure specific to Irritable Bowel Syndrome (IBS) that can be used to assess the impact of IBS and its treatment. The IBS-QOL was measured at baseline, week 12 and week 24. The individual responses to the 34 items are summed and averaged for a total score and then transformed to a 0-100 scale for ease of interpretation with higher scores indicating better IBS specific quality of life. |
| Bowel Symptom Score (BSS) Amongst Subgroups | 12 weeks | Median (average) BSS amongst the different IBS subgroups (diarrhea, constipation, pain, and bloating). The BSS is a 100-mm visual analog scale for the different symptoms of IBS (pain/discomfort, constipation, diarrhea, and overall severity). Symptoms on the BSS can range from 0 = no pain to 100 = extreme pain. |
| IBS Symptoms Moderately or a Lot Better | 24 weeks | Number of participants who stated their IBS symptoms were moderately better or a lot better at 24 weeks. |
| Bowel Symptom Score (BSS) at 24 Weeks | 24 weeks | The BSS is a five question, 100-mm visual analog scale of four IBS symptoms (pain/discomfort, bloating, constipation, and diarrhea), and an overall severity scale. The best possible value would be 0 (no symptoms) and the worst is 500 (severe symptoms). BSS was assessed on a bi-weekly basis. |
| Center for Epidemiologic Studies Depression Scale (CES-D) Score | 12 weeks | We measured CES-D Score at baseline as well as bi-weekly throughout the study. The CES-D is a self-reported 20 question survey designed to measure depressive symptomatology in the general population. The possible range of scores is zero to 60, with the higher scores indicating the presence of more symptomatology. |
Countries
United States
Participant flow
Recruitment details
Participants were identified through community, institutional advertisement, clinicaltrials.gov, through the IFFGD webpage as well as through the outpatient clinics beginning in February 2006. Participants who participated in previous IBS studies were also mailed a recruitment letter to ask if they would be interested in participating.
Pre-assignment details
For this study, there was a 2-week screening and enrollment phase. During this period, participants were screened, a symptom questionnaire was completed, and there was a physician exam. After the in-person screening visit, a phone call was made prior to mailing the study materials to ensure the participant was still willing to participate.
Participants by arm
| Arm | Count |
|---|---|
| St. John's Wort St. John's Wort, 450 mg twice a day | 35 |
| Placebo Placebo, twice a day | 35 |
| Total | 70 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 2 |
| Overall Study | Withdrawal by Subject | 3 | 3 |
Baseline characteristics
| Characteristic | St. John's Wort | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 0 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 33 Participants | 35 Participants | 68 Participants |
| Age Continuous | 42.2 years STANDARD_DEVIATION 14.34 | 39.43 years STANDARD_DEVIATION 11.26 | 40.81 years STANDARD_DEVIATION 12.87 |
| Bowel Symptom Score (BSS) | 173 Units on a scale | 165 Units on a scale | 169 Units on a scale |
| Center for Epidemiologic Studies Depression Scale (CES-D) score | 6 Units on a scale | 5 Units on a scale | 5.5 Units on a scale |
| Irritable Bowel Syndrome - Quality of Life (IBS-QoL) | 23 Units on a scale | 20 Units on a scale | 21.5 Units on a scale |
| Region of Enrollment United States | 35 participants | 35 participants | 70 participants |
| Sex: Female, Male Female | 30 Participants | 30 Participants | 60 Participants |
| Sex: Female, Male Male | 5 Participants | 5 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 35 | 0 / 35 |
| serious Total, serious adverse events | 0 / 35 | 0 / 35 |
Outcome results
Primary
Overall Bowel Symptom Scores (BSS)
The primary end point was the overall self-reported BSS after 12 weeks of therapy for all randomized participants to assess for differences between treatment groups at the end of the treatment period (12 weeks). The BSS is a 100-mm visual analog scale for the different symptoms of IBS (pain/discomfort, constipation, diarrhea, and overall severity). Symptoms on the BSS can range from 0 = no pain to 100 = extreme pain.
Time frame: After 12 weeks of treatment
Population: Analysis is based on the intention to treat (ITT) paradigm, including all randomized patients. Assuming standard deviation of the overall BSS symptom score is \~75, then 35 per group provides 80% power to detect about a 50% difference which is based on a 2-sample t-test assuming the distribution of Bowel Symptom Survey (BSS) values.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| St. John's Wort | Overall Bowel Symptom Scores (BSS) | 76 Scores on a scale |
| Placebo | Overall Bowel Symptom Scores (BSS) | 44 Scores on a scale |
Secondary
Adequate Relief ≤ 50% During the Last 4 Weeks of Therapy
Participants who reported yes or no to having adequate relief of their IBS symptoms at least 50% during the last 4 weeks of therapy.
Time frame: Last 4 weeks of therapy
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| St. John's Wort | Adequate Relief ≤ 50% During the Last 4 Weeks of Therapy | Yes | 32 Percentage of Participants |
| St. John's Wort | Adequate Relief ≤ 50% During the Last 4 Weeks of Therapy | No | 50 Percentage of Participants |
| St. John's Wort | Adequate Relief ≤ 50% During the Last 4 Weeks of Therapy | Missing | 18 Percentage of Participants |
| Placebo | Adequate Relief ≤ 50% During the Last 4 Weeks of Therapy | Yes | 62 Percentage of Participants |
| Placebo | Adequate Relief ≤ 50% During the Last 4 Weeks of Therapy | No | 26 Percentage of Participants |
| Placebo | Adequate Relief ≤ 50% During the Last 4 Weeks of Therapy | Missing | 12 Percentage of Participants |
Secondary
Bowel Symptom Score (BSS) Amongst Subgroups
Median (average) BSS amongst the different IBS subgroups (diarrhea, constipation, pain, and bloating). The BSS is a 100-mm visual analog scale for the different symptoms of IBS (pain/discomfort, constipation, diarrhea, and overall severity). Symptoms on the BSS can range from 0 = no pain to 100 = extreme pain.
Time frame: 12 weeks
Population: Analysis is based on the intention to treat (ITT) paradigm, including all randomized patients. Assuming standard deviation of the overall BSS symptom score is \~75, then 35 per group provides 80% power to detect about a 50% difference which is based on a 2-sample t-test assuming the distribution of Bowel Symptom Survey (BSS) values.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| St. John's Wort | Bowel Symptom Score (BSS) Amongst Subgroups | BSS for diarrhea subgroup | 32 Scores on a scale |
| St. John's Wort | Bowel Symptom Score (BSS) Amongst Subgroups | BSS for constipation subgroup | 25.8 Scores on a scale |
| St. John's Wort | Bowel Symptom Score (BSS) Amongst Subgroups | BSS for pain subgroup | 35.8 Scores on a scale |
| St. John's Wort | Bowel Symptom Score (BSS) Amongst Subgroups | BSS for bloating subgroup | 30.3 Scores on a scale |
| Placebo | Bowel Symptom Score (BSS) Amongst Subgroups | BSS for bloating subgroup | 23.8 Scores on a scale |
| Placebo | Bowel Symptom Score (BSS) Amongst Subgroups | BSS for diarrhea subgroup | 17 Scores on a scale |
| Placebo | Bowel Symptom Score (BSS) Amongst Subgroups | BSS for pain subgroup | 23.5 Scores on a scale |
| Placebo | Bowel Symptom Score (BSS) Amongst Subgroups | BSS for constipation subgroup | 16 Scores on a scale |
Secondary
Bowel Symptom Score (BSS) at 24 Weeks
The BSS is a five question, 100-mm visual analog scale of four IBS symptoms (pain/discomfort, bloating, constipation, and diarrhea), and an overall severity scale. The best possible value would be 0 (no symptoms) and the worst is 500 (severe symptoms). BSS was assessed on a bi-weekly basis.
Time frame: 24 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| St. John's Wort | Bowel Symptom Score (BSS) at 24 Weeks | 65 Units on a scale |
| Placebo | Bowel Symptom Score (BSS) at 24 Weeks | 60 Units on a scale |
Secondary
Center for Epidemiologic Studies Depression Scale (CES-D) Score
We measured CES-D Score at baseline as well as bi-weekly throughout the study. The CES-D is a self-reported 20 question survey designed to measure depressive symptomatology in the general population. The possible range of scores is zero to 60, with the higher scores indicating the presence of more symptomatology.
Time frame: 12 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| St. John's Wort | Center for Epidemiologic Studies Depression Scale (CES-D) Score | 2 Units on a scale |
| Placebo | Center for Epidemiologic Studies Depression Scale (CES-D) Score | 3 Units on a scale |
Secondary
Center for Epidemiologic Studies Depression Scale (CES-D) Score
We measured CES-D Score at baseline as well as bi-weekly throughout the study. The CES-D is a self-reported 20 question survey designed to measure depressive symptomatology in the general population. The possible range of scores is zero to 60, with the higher scores indicating the presence of more symptomatology.
Time frame: 24 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| St. John's Wort | Center for Epidemiologic Studies Depression Scale (CES-D) Score | 3.0 Units on a scale |
| Placebo | Center for Epidemiologic Studies Depression Scale (CES-D) Score | 2.5 Units on a scale |
Secondary
IBS Symptoms Moderately or a Lot Better
Number of participants who stated their IBS symptoms were moderately better or a lot better at 24 weeks.
Time frame: 24 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| St. John's Wort | IBS Symptoms Moderately or a Lot Better | Yes | 5 participants |
| St. John's Wort | IBS Symptoms Moderately or a Lot Better | No | 24 participants |
| St. John's Wort | IBS Symptoms Moderately or a Lot Better | Missing | 6 participants |
| Placebo | IBS Symptoms Moderately or a Lot Better | Yes | 5 participants |
| Placebo | IBS Symptoms Moderately or a Lot Better | No | 25 participants |
| Placebo | IBS Symptoms Moderately or a Lot Better | Missing | 5 participants |
Secondary
Irritable Bowel Syndrome - Quality of Life (IBS-QoL) Score
The IBS-QOL is a self-report quality-of-life measure specific to Irritable Bowel Syndrome (IBS) that can be used to assess the impact of IBS and its treatment. The IBS-QOL was measured at baseline, week 12 and week 24. The individual responses to the 34 items are summed and averaged for a total score and then transformed to a 0-100 scale for ease of interpretation with higher scores indicating better IBS specific quality of life.
Time frame: 12 weeks of treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| St. John's Wort | Irritable Bowel Syndrome - Quality of Life (IBS-QoL) Score | 18.8 Units on a scale |
| Placebo | Irritable Bowel Syndrome - Quality of Life (IBS-QoL) Score | 14.7 Units on a scale |