A Placebo-Controlled Trial of St. John's Wort for Irritable Bowel Syndrome

• Sponsor: Mayo Clinic (Other)
• Overall Status: Completed
• CT.gov ID: NCT00587860
• Collaborator: (none)
• Enrollment: 70
• Location: 1
• Arms: 2
• Duration (Months): 24.9
• Patients Per Site Per Month: 2.8

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Irritable Bowel Syndrome	Drug: St. John's wort; Drug: Placebo	Phase 2

Detailed Description

Eligibility criteria:

1. Established diagnosis of IBS

2. 18-70 years of age

1. 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 70 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Placebo-Controlled Trial of St. John's Wort for Irritable Bowel Syndrome
• Study Start Date: Feb 1, 2006
• Actual Primary Completion Date: Jan 1, 2008
• Actual Study Completion Date: Mar 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo	Drug: Placebo; Dosage form: Tablet (450 mg) Dose: 450 mg twice a day, placebo twice a day
Active Comparator: St. John's Wort	Drug: St. John's wort; Dosage form: Tablet (450 mg) Dose: 450 mg twice a day, placebo twice a day; Other Names: Latin name: Hypericum perforatum L. Common name: St. John's Wort

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. Center for Epidemiologic Studies Depression Scale (CES-D) Score [24 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.

7. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts 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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Rochester	Minnesota	United States	55902

Sponsors and Collaborators

• Mayo Clinic

Investigators

• Principal Investigator: Yuri A. Saito Loftus, M.D. M.P.H., Mayo Clinic

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Mayo Clinic Clinical Trials

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00587860
• Other Study ID Numbers: 132-06
• First Posted: Jan 8, 2008
• Last Update Posted: Mar 9, 2010
• Last Verified: Mar 1, 2010

• Additional relevant MeSH terms: Irritable Bowel Syndrome; Syndrome

Study Results

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 Detail	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.

Arm/Group Title	St. John's Wort	Placebo
Arm/Group Description	St. John's Wort, 450 mg twice a day	Placebo, twice a day
Period Title: Overall Study
STARTED	35	35
COMPLETED	30	30
NOT COMPLETED	5	5

Baseline Characteristics

Arm/Group Title	St. John's Wort	Placebo	Total
Arm/Group Description	St. John's Wort, 450 mg twice a day	Placebo, twice a day	Total of all reporting groups
Overall Participants	35	35	70
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	33 94.3%	35 100%	68 97.1%
>=65 years	2 5.7%	0 0%	2 2.9%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	42.2 (14.34)	39.43 (11.26)	40.81 (12.87)
Sex: Female, Male (Count of Participants)
Female	30 85.7%	30 85.7%	60 85.7%
Male	5 14.3%	5 14.3%	10 14.3%
Region of Enrollment (participants) [Number]
United States	35 100%	35 100%	70 100%
Bowel Symptom Score (BSS) (Units on a scale) [Median (Full Range) ]
Median (Full Range) [Units on a scale]	173	165	169
Center for Epidemiologic Studies Depression Scale (CES-D) score (Units on a scale) [Median (Full Range) ]
Median (Full Range) [Units on a scale]	6	5	5.5
Irritable Bowel Syndrome - Quality of Life (IBS-QoL) (Units on a scale) [Median (Full Range) ]
Median (Full Range) [Units on a scale]	23	20	21.5

Outcome Measures

1. Primary Outcome

Title	Overall Bowel Symptom Scores (BSS)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	St. John's Wort	Placebo
Arm/Group Description	St. John's Wort, 450 mg twice a day	Placebo, twice a day
Measure Participants	35	35
Median (Full Range) [Scores on a scale]	76	44

2. Secondary Outcome

Title	Bowel Symptom Score (BSS) Amongst Subgroups
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	St. John's Wort	Placebo
Arm/Group Description	St. John's Wort, 450 mg twice a day	Placebo, twice a day
Measure Participants	35	35
BSS for diarrhea subgroup	32	17
BSS for constipation subgroup	25.8	16
BSS for pain subgroup	35.8	23.5
BSS for bloating subgroup	30.3	23.8

3. Secondary Outcome

Title	Adequate Relief ≤ 50% During the Last 4 Weeks of Therapy
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	St. John's Wort	Placebo
Arm/Group Description	St. John's Wort, 450 mg twice a day	Placebo, twice a day
Measure Participants	35	35
Yes	32 91.4%	62 177.1%
No	50 142.9%	26 74.3%
Missing	18 51.4%	12 34.3%

4. Secondary Outcome

Title	Irritable Bowel Syndrome - Quality of Life (IBS-QoL) Score
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	St. John's Wort	Placebo
Arm/Group Description	St. John's Wort, 450 mg twice a day	Placebo, twice a day
Measure Participants	35	35
Median (Full Range) [Units on a scale]	18.8	14.7

5. Secondary Outcome

Title	Center for Epidemiologic Studies Depression Scale (CES-D) Score
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	St. John's Wort	Placebo
Arm/Group Description	St. John's Wort, 450 mg twice a day	Placebo, twice a day
Measure Participants	35	35
Median (Full Range) [Units on a scale]	2	3

6. Secondary Outcome

Title	IBS Symptoms Moderately or a Lot Better
Description	Number of participants who stated their IBS symptoms were moderately better or a lot better at 24 weeks.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	St. John's Wort	Placebo
Arm/Group Description	St. John's Wort, 450 mg twice a day	Placebo, twice a day
Measure Participants	35	35
Yes	5 14.3%	5 14.3%
No	24 68.6%	25 71.4%
Missing	6 17.1%	5 14.3%

7. Secondary Outcome

Title	Center for Epidemiologic Studies Depression Scale (CES-D) Score
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	St. John's Wort	Placebo
Arm/Group Description	St. John's Wort, 450 mg twice a day	Placebo, twice a day
Measure Participants	35	35
Median (Full Range) [Units on a scale]	3.0	2.5

8. Secondary Outcome

Title	Bowel Symptom Score (BSS) at 24 Weeks
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	St. John's Wort	Placebo
Arm/Group Description	St. John's Wort, 450 mg twice a day	Placebo, twice a day
Measure Participants	35	35
Median (Full Range) [Units on a scale]	65	60

Adverse Events

Time Frame	Study duration
Adverse Event Reporting Description	Patients will be evaluated on a bi-weekly basis by phone interview and paper questionnaire. During these queries, subjects will be asked to report study medication compliance and side effects or adverse events (AE). Adverse events will be categorized into Serious Adverse Events (SAE) and Non-serious Adverse Events (NAE).
Arm/Group Title	St. John's Wort		Placebo
Arm/Group Description	St. John's Wort, 450 mg twice a day		Placebo, twice a day
All Cause Mortality
	St. John's Wort		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	St. John's Wort		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/35 (0%)		0/35 (0%)
Other (Not Including Serious) Adverse Events
	St. John's Wort		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/35 (0%)		0/35 (0%)

Limitations/Caveats

A majority of the participants were local females with mild symptoms The number of participants limits power of conclusions We evaluated the efficacy of SJW in all subtypes of IBS not allowing specific conclusions regarding subtypes

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.