Ignite Creation Date:
2024-05-05 @ 11:47 AM
Last Modification Date:
2024-10-26 @ 9:13 AM
Study NCT ID:
NCT00130741
Status:
COMPLETED
Last Update Posted:
2007-04-11
First Post:
2005-08-15
Brief Title:
Combination Herbal Therapy CHT Versus Placebo in Patients With Irritable Bowel Syndrome IBS
Sponsor:
Hadassah Medical Organization
Organization:
Hadassah Medical Organization
Study Overview
Official Title:
A Phase I Double-Blind Placebo-Controlled Randomized Parallel-Group Study to Evaluate the Safety and Efficacy of a Combination Herbal Therapy CHT Versus Placebo in Improving the Overall Quality of Life and Symptoms in Patients With Irritable Bowel Syndrome IBS
Status:
COMPLETED
Status Verified Date:
2007-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This is an 8-week double-blind placebo-controlled randomized parallel-group study with an additional two week baseline observation period to evaluate the safety of combination herbal therapy CHT versus placebo and short and long-term efficacy in terms of improved IBS overall quality of life QOL and symptomatology
Detailed Description:
Background
IBS Irritable Bowel Syndrome is a disorder of motility of the entire GI tract that produces cramping abdominal pain constipation andor diarrhea and sometimes passing of mucus in bowel movements In most people with IBS the GI tract is highly sensitive to many stimuli including diet and distension from gas Among dietary suspects are high-fat or other high-calorie meals dairy products wheat citrus fruits coffee and tea which can trigger spasms of the colon muscle During an episode GI tract contractions become stronger and more frequent and the resulting rapid motility may lead to diarrhea When colon motility is reduced bowel movements do not occur regularly resulting in constipation Cramping appears to be induced by strong contractions and increased sensitivity of pain receptors in the large intestine IBS can be triggered or intensified by stress due to communications between the central nervous system and the nervous system of the small and large intestines This is sometimes referred to as a brain-gut connection and is supported by inspection of electroencephalogram EEG traces which showed significantly greater EEG abnormality in IBS patients 292 than in controls 42 p002 The degree of abnormality was positively correlated with colonic motility only in IBS patients p005 allowing the authors to conclude that there is an electrophysiologic brain-gut interaction in IBS
IBS can cause great physical discomfort and embarrassment to many of its sufferers but is not life threatening
There is no current consensus as to an organic cause of this syndrome and there generally appears to be no sign of disease upon physical examination except for tenderness over the large intestine The diagnosis is symptom-based usually through identification of the ROME II criteria for IBS These criteria which have been accepted worldwide by clinicians and researchers as the standard for IBS diagnosis are as follows At least 12 weeks which need not be consecutive in the preceding 12 months of abdominal discomfort or pain that has two of three features
Relieved with defecation andor
Onset associated with a change in frequency of stool andor
Onset associated with a change in form appearance of stool
In addition the following symptoms cumulatively support the diagnosis of IBS
Abnormal stool frequency for research purposes abnormal may be defined as 3day and 3week
Abnormal stool form lumpyhard or loose watery stool
Abnormal stool passage straining urgency or feeling of incomplete evacuation
Passage of mucus
Bloating or feeling of abdominal distension
The prevalence rate of IBS in 1998 in the US was approximately 5700 cases per 100000 persons with a much higher rate in Caucasians than in Hispanics or Afro-Americans The total direct cost of IBS including costs of inpatient and outpatient health services utilization and prescription medication was greater than 16 billion annually in 1998 in the US while the indirect costs primarily absenteeism from work are estimated at over 20 billion 1 AGA The burden of gastrointestinal diseases IBS is treated primarily in the physicians office with patient education assurance andor dietary and lifestyle modifications being the rule for mild cases but prescription medicines being offered in more moderate cases Prescription therapy for theses patients generally falls under two categories - drugs affecting gut physiology and psychological treatment Very severe cases may be treated by centrally-acting agents ie tricyclic antidepressants TCAs or selective serotonin reuptake inhibitors together with psychological methods
Among the medications generally used to affect gut physiology or abdominal pain are antispasmodics tricyclic antidepressants TCAs loperamide Cholestyramine for patients with cholecystectomy or who may have idiopathic bile acid malabsorption and serotonergic agents 5-HT3 receptor antagonists and 5-HT4 receptor agonists These agents show relative success in improving individual symptoms only and are only effective in specific subgroups of patients eg- for diarrhea-predominant but not constipation-predominant IBS or visa versa Due to the heterogeneity of IBS an effective therapy for one may often lead to deterioration in another For example Alosetron an extensively studied 5-HT3 antagonist which has shown statistically significant improvement in women with diarrhea-predominant IBS causes constipation in 20-30 of patients and there has been no clear evidence of a benefit for men
There are many known side effects of anticholinergic antispasmodics and TCAs such as headache dry mouth cough blurred vision constipation dysuria postural hypotension tachycardia decreased libido erectile failure increased sensitivity to the sun weight gain sedation increased sweating Loperamide side effects include Stomach ache nausea vomiting bloating constipation dry mouth drowsiness or dizziness and cholestyramine has been known to cause constipation heartburn indigestion nausea vomiting and stomach pain and has caused tumors in animal studies These profiles suggest the need for a safer more tolerable and more comprehensive therapy for IBS
Psychological treatments are initiated when symptoms are severe enough to impair health-related quality of life Mental health referral may also be made for treatment of associated psychiatric disorders such as major depression These methods include cognitive-behavioral treatment dynamic interpersonal psychotherapy hypnosis and stress managementrelaxation Though benefit has been seen with these therapeutic methods in the relief of abdominal pain diarrhea and anxiety constipation has not been improved and the effect on various subgroups of patients has not been investigated 4 AGA Med Pos Stat
CHT
Some Botanical therapies specifically combination therapies have been tested for treatment of IBS with positive results STW 5 9 plant extracts and STW 5-II 6 plant extracts were significantly better than placebo in reducing abdominal pain and IBS symptoms after 4 weeks of therapy
Additionally various botanical therapies have been shown to be effective to different degrees for relief of symptoms and for improved quality of life in non-ulcer and functional dyspepsia a condition similar to IBS These include the following therapies tested in trials which received a rating above three in the Jadad score a validated instrument scoring from 0-5 for assessment of clinical trial quality celandine extract turmeric peppermint and caraway oils Iberogast peppermint leaves caraway fruit with or without bitter candy tuft fruit licorice root lemon balm leaves angelica root celandine herbs milk thistle fruit and chamomile flowers peppermint caraway wormwood fennel peppermint oil and ginger extract artichoke leaf extract and many others with lower Jadad score ratings
A number of herbs have been used successfully in IBS as well These include peppermint oil enteric coated globe artichoke leaf extract and Chinese herbal medicine
The active ingredients of CHT has been used in folklore medicine for many centuries for treatment of gastrointestinal diseases and is approved by the Israel Ministry of Health for marketing and distribution through the pharmacy A dose toxicity test conducted in rats showed a no-observed-adverse-effect-level in male rats at doses much higher than the dose utilized in this study measured per Kg body mass
Considering the ethno-pharmacological and preclinical evidence for efficacy in a broad array of conditions and safety of the principal active ingredient we the investigators at Hadassah Medical Organization have decided to embark upon a clinical development plan geared towards the investigation of the gastrointestinal protective and other therapeutic properties and safety of the principal active ingredient The first study is the efficacy trial herein described
Rationale for the study
HCT is a new combination botanical drug substance that promises to be of value in treating various pathologies of the gastrointestinal tract due to its presumed gastroprotective andor gastrosynchronic qualities To test this hypothesis a once daily oral dose of HCT will be self-administered to patients with IBS The dose used is presumed to be exceptionally safe and is 37 times lower than the standard daily dose
STUDY OBJECTIVE
To determine the safety tolerability and effectiveness of 25 mg per day of HCT 20 mg principal active ingredient compared to placebo in subjects with ROME II IBS criteria
Basic Design Characteristics and Rationale
This will be a double-blind placebo-controlled randomized parallel group study to assess the safety and efficacy of CHT 100 subjects with ROME II criteria IBS will provide informed consent and undergo screening procedures Subjects fulfilling eligibility requirements will be randomized to one of the two treatment arms will receive a subject number After a two-week baseline observation period and reconfirmed eligibility subjects will be allotted enough study drug for the self administration of a daily dose of 25 mg CHT or placebo for 4 weeks The Week 4 clinic visit will be followed by a four week follow-up period without treatment The day of randomization will be the week -2 visit and start of study treatment will be at the Week 0 study visit
Throughout the study the following tools will be utilized and variables assessed a subject diary for documentation of concomitant medications and concomitant medication changes and adverse events the IBS-36 Questionnaire for assessment of treatment-induced changes in the IBS-specific Quality of Life score and a 6-point Likert Scale for IBS symptoms severity scoring This tool and has been developed specifically for this study based in part on similar scales in the published literature
This early phase study is well-designed to investigate the safety and tolerability of HCT and to gain statistically significant efficacy data The population chosen is large enough to detect a clinically significant difference in response between the active study drug and the placebo arms The rationale for this design at such an early stage of development is based upon the recommendations of the FDA for phase I clinical studies of botanical drug substances
IBS Irritable Bowel Syndrome is a disorder of motility of the entire GI tract that produces cramping abdominal pain constipation andor diarrhea and sometimes passing of mucus in bowel movements In most people with IBS the GI tract is highly sensitive to many stimuli including diet and distension from gas Among dietary suspects are high-fat or other high-calorie meals dairy products wheat citrus fruits coffee and tea which can trigger spasms of the colon muscle During an episode GI tract contractions become stronger and more frequent and the resulting rapid motility may lead to diarrhea When colon motility is reduced bowel movements do not occur regularly resulting in constipation Cramping appears to be induced by strong contractions and increased sensitivity of pain receptors in the large intestine IBS can be triggered or intensified by stress due to communications between the central nervous system and the nervous system of the small and large intestines This is sometimes referred to as a brain-gut connection and is supported by inspection of electroencephalogram EEG traces which showed significantly greater EEG abnormality in IBS patients 292 than in controls 42 p002 The degree of abnormality was positively correlated with colonic motility only in IBS patients p005 allowing the authors to conclude that there is an electrophysiologic brain-gut interaction in IBS
IBS can cause great physical discomfort and embarrassment to many of its sufferers but is not life threatening
There is no current consensus as to an organic cause of this syndrome and there generally appears to be no sign of disease upon physical examination except for tenderness over the large intestine The diagnosis is symptom-based usually through identification of the ROME II criteria for IBS These criteria which have been accepted worldwide by clinicians and researchers as the standard for IBS diagnosis are as follows At least 12 weeks which need not be consecutive in the preceding 12 months of abdominal discomfort or pain that has two of three features
Relieved with defecation andor
Onset associated with a change in frequency of stool andor
Onset associated with a change in form appearance of stool
In addition the following symptoms cumulatively support the diagnosis of IBS
Abnormal stool frequency for research purposes abnormal may be defined as 3day and 3week
Abnormal stool form lumpyhard or loose watery stool
Abnormal stool passage straining urgency or feeling of incomplete evacuation
Passage of mucus
Bloating or feeling of abdominal distension
The prevalence rate of IBS in 1998 in the US was approximately 5700 cases per 100000 persons with a much higher rate in Caucasians than in Hispanics or Afro-Americans The total direct cost of IBS including costs of inpatient and outpatient health services utilization and prescription medication was greater than 16 billion annually in 1998 in the US while the indirect costs primarily absenteeism from work are estimated at over 20 billion 1 AGA The burden of gastrointestinal diseases IBS is treated primarily in the physicians office with patient education assurance andor dietary and lifestyle modifications being the rule for mild cases but prescription medicines being offered in more moderate cases Prescription therapy for theses patients generally falls under two categories - drugs affecting gut physiology and psychological treatment Very severe cases may be treated by centrally-acting agents ie tricyclic antidepressants TCAs or selective serotonin reuptake inhibitors together with psychological methods
Among the medications generally used to affect gut physiology or abdominal pain are antispasmodics tricyclic antidepressants TCAs loperamide Cholestyramine for patients with cholecystectomy or who may have idiopathic bile acid malabsorption and serotonergic agents 5-HT3 receptor antagonists and 5-HT4 receptor agonists These agents show relative success in improving individual symptoms only and are only effective in specific subgroups of patients eg- for diarrhea-predominant but not constipation-predominant IBS or visa versa Due to the heterogeneity of IBS an effective therapy for one may often lead to deterioration in another For example Alosetron an extensively studied 5-HT3 antagonist which has shown statistically significant improvement in women with diarrhea-predominant IBS causes constipation in 20-30 of patients and there has been no clear evidence of a benefit for men
There are many known side effects of anticholinergic antispasmodics and TCAs such as headache dry mouth cough blurred vision constipation dysuria postural hypotension tachycardia decreased libido erectile failure increased sensitivity to the sun weight gain sedation increased sweating Loperamide side effects include Stomach ache nausea vomiting bloating constipation dry mouth drowsiness or dizziness and cholestyramine has been known to cause constipation heartburn indigestion nausea vomiting and stomach pain and has caused tumors in animal studies These profiles suggest the need for a safer more tolerable and more comprehensive therapy for IBS
Psychological treatments are initiated when symptoms are severe enough to impair health-related quality of life Mental health referral may also be made for treatment of associated psychiatric disorders such as major depression These methods include cognitive-behavioral treatment dynamic interpersonal psychotherapy hypnosis and stress managementrelaxation Though benefit has been seen with these therapeutic methods in the relief of abdominal pain diarrhea and anxiety constipation has not been improved and the effect on various subgroups of patients has not been investigated 4 AGA Med Pos Stat
CHT
Some Botanical therapies specifically combination therapies have been tested for treatment of IBS with positive results STW 5 9 plant extracts and STW 5-II 6 plant extracts were significantly better than placebo in reducing abdominal pain and IBS symptoms after 4 weeks of therapy
Additionally various botanical therapies have been shown to be effective to different degrees for relief of symptoms and for improved quality of life in non-ulcer and functional dyspepsia a condition similar to IBS These include the following therapies tested in trials which received a rating above three in the Jadad score a validated instrument scoring from 0-5 for assessment of clinical trial quality celandine extract turmeric peppermint and caraway oils Iberogast peppermint leaves caraway fruit with or without bitter candy tuft fruit licorice root lemon balm leaves angelica root celandine herbs milk thistle fruit and chamomile flowers peppermint caraway wormwood fennel peppermint oil and ginger extract artichoke leaf extract and many others with lower Jadad score ratings
A number of herbs have been used successfully in IBS as well These include peppermint oil enteric coated globe artichoke leaf extract and Chinese herbal medicine
The active ingredients of CHT has been used in folklore medicine for many centuries for treatment of gastrointestinal diseases and is approved by the Israel Ministry of Health for marketing and distribution through the pharmacy A dose toxicity test conducted in rats showed a no-observed-adverse-effect-level in male rats at doses much higher than the dose utilized in this study measured per Kg body mass
Considering the ethno-pharmacological and preclinical evidence for efficacy in a broad array of conditions and safety of the principal active ingredient we the investigators at Hadassah Medical Organization have decided to embark upon a clinical development plan geared towards the investigation of the gastrointestinal protective and other therapeutic properties and safety of the principal active ingredient The first study is the efficacy trial herein described
Rationale for the study
HCT is a new combination botanical drug substance that promises to be of value in treating various pathologies of the gastrointestinal tract due to its presumed gastroprotective andor gastrosynchronic qualities To test this hypothesis a once daily oral dose of HCT will be self-administered to patients with IBS The dose used is presumed to be exceptionally safe and is 37 times lower than the standard daily dose
STUDY OBJECTIVE
To determine the safety tolerability and effectiveness of 25 mg per day of HCT 20 mg principal active ingredient compared to placebo in subjects with ROME II IBS criteria
Basic Design Characteristics and Rationale
This will be a double-blind placebo-controlled randomized parallel group study to assess the safety and efficacy of CHT 100 subjects with ROME II criteria IBS will provide informed consent and undergo screening procedures Subjects fulfilling eligibility requirements will be randomized to one of the two treatment arms will receive a subject number After a two-week baseline observation period and reconfirmed eligibility subjects will be allotted enough study drug for the self administration of a daily dose of 25 mg CHT or placebo for 4 weeks The Week 4 clinic visit will be followed by a four week follow-up period without treatment The day of randomization will be the week -2 visit and start of study treatment will be at the Week 0 study visit
Throughout the study the following tools will be utilized and variables assessed a subject diary for documentation of concomitant medications and concomitant medication changes and adverse events the IBS-36 Questionnaire for assessment of treatment-induced changes in the IBS-specific Quality of Life score and a 6-point Likert Scale for IBS symptoms severity scoring This tool and has been developed specifically for this study based in part on similar scales in the published literature
This early phase study is well-designed to investigate the safety and tolerability of HCT and to gain statistically significant efficacy data The population chosen is large enough to detect a clinically significant difference in response between the active study drug and the placebo arms The rationale for this design at such an early stage of development is based upon the recommendations of the FDA for phase I clinical studies of botanical drug substances
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None