PouchitisPhase 2NCT00583076
Safety and Efficacy of AST-120 in the Treatment of Pouchitis
A Phase 2 study testing AST-120 in people with Pouchitis, run by Ocera Therapeutics at 1 site in United States.
Trial summary
The aim of the study is to assess the safety and efficacy of an investigational agent, AST-120, in treating patients with active pouchitis. This is an open-label trial which means that all patients will receive AST-120 in 2g sachets (packets)three times a day for 4 weeks. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Pouchitis
- What is being tested?
- AST-120
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2007to May 2008
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with a current episode of active pouchitis (defined as having a PDAI score > 7) after IPAA for UC confirmed by endoscopy and histology
- Patients with active pouchitis who have never been treated with antibiotics (antibiotic-naive) or who have been previously treated with antibiotics and responded. Antibiotic-dependent patients may be enrolled as long as antibiotic use is discontinued for at least two weeks prior to study entry. Antibiotic-dependent pouchitis is defined as a condition in which a patient with frequent episodes (> or = 4 episodes per year) of pouchitis or persistent symptoms requires long-term, continuous antibiotic or probiotic therapy to keep the disease in remission.
- Able to give informed consent
- Able and willing to comply with all study procedures
- Females must be post-menopausal, surgically incapable of bearing children, or practicing a reliable single barrier method of birth control (condom, intrauterine devices, spermicide and barrier, Depot). Partner/spouse sterility may also qualify at the investigator's discretion. Females of child-bearing potential must have a negative urine pregnancy test at baseline. Oral contraceptives are not acceptable as there is a potential interaction with AST-120.
Who cannot join
- Patients previously treated with infliximab or any investigational immunosuppressant/immunomodulator
- Patients whose condition is severe enough that, in the investigator's opinion, withholding antibiotics for 4 weeks during the AST-120 trial is not feasible
- Patients undergoing chemotherapy for the treatment of cancer
- Antibiotic use within 2 weeks prior to the entry of the study
- Crohn's disease of the pouch, including inflammatory, fibrostenotic, or fistulizing phenotypes, based on the previously established diagnostic criteria (Shen B, et al. Am J Gastroenterol 2006 in press)
- Active specific infection of the pouch: cytomegalovirus infection and C. difficile infection
Show all 21Show fewer
- Patients with chronic antibiotic-refractory pouchitis. Antibiotic- refractory pouchitis is defined as a condition where a patient fails to respond to a 4 week course of a single antibiotic (metronidazole or ciprofloxacin), requiring prolonged therapy of > or = 4 weeks consisting of 2 antibiotics, oral or topical 5-aminosalicylate, corticosteroid therapy, or oral immunomodulator therapy.
- History of non-inflammatory disease of the pouch: decreased pouch compliance, irritable pouch syndrome, afferent or efferent limb obstruction
- Isolated cuffitis. Patients who have active pouchitis as the predominant condition, but also have cuffitis may be enrolled.
- Strictures of the pouch inlet or outlet
- Ileal pouch patients with familial adenomatous polyposis
- History of lactose intolerance
- Known celiac disease
- Primary sclerosing cholangitis (PSC) with or without liver transplant; PSC with or without Actigall or Urso therapy
- Uncontrolled systemic diseases
- Needing oral or topical steroid treatment or 5-ASA agents
- Other major physical or major psychiatric illness within the last 6 months that in the opinion of the investigator would affect the patient's ability to complete the trial
- Active use of cholestyramine
- Active use of NSAIDs or aspirin
- Women who are pregnant, breast feeding, or planning to become pregnant during the study
- Patients who are on therapy of 5-ASA at the entry of the study
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Pilot Study of the Safety and Efficacy of AST-120 in the Treatment of Active Pouchitis
The aim of the study is to assess the safety and efficacy of an investigational agent, AST-120, in treating patients with active pouchitis. This is an open-label trial which means that all patients will receive AST-120 in 2g sachets (packets)three times a day for 4 weeks. All antibiotics, probiotics and nutritional agents must have been discontinued for at least 2 weeks prior to study entry. An initial group of 10 patients will be enrolled. If there are no serious adverse events associated with the study drug and at least 3 of the 10 patients respond, a second group of 10 patients will be enrolled. In the second group of patients, those patients who are considered responders or who are in remission are eligible to receive open-label AST-120 for as long as response is maintained up to a maximum of 52 weeks. Patients will have clinic visits at the start of the study and at week 4. If continuing on open label AST-120 after week 4, patients will have clinic visits every 12 weeks to assess the continuing safety and efficacy of AST-120. Endoscopies will be performed at the start of the study, week 4, week 28, week 52 or early termination.
Read the detailed description
The management and prognosis vary in different types of pouchitis. For antibiotic-responsive pouchitis, the first-line therapy includes a 2-week course of metronidazole or ciprofloxacin. A relapsing course of pouchitis is common. Of the patients with acute pouchitis, 61% would develop at least one recurrence. Typically, patient's symptoms and endoscopic and histologic inflammation respond favorably to antibiotic therapy, but symptoms quickly recur when antibiotics are discontinued. This group of patients is classified as having antibiotic-dependent pouchitis and often requires long-term antibiotic or probiotic therapy to keep the disease in remission.
Although the majority of patients with active pouchitis respond favorably to antibiotic therapy, relapse is common, which often requires frequent antibiotic therapy. The concerns about frequent use of antibiotic agents are: 1)antibiotics such as metronidazole often cause adverse effects; 2)long-term or frequent use of antibiotics, including ciprofloxacin, metronidazole, and rifaximin, often leads to bacterial resistance. In clinical practice, we have encountered more and more patients with antibiotic-refractory pouchitis, which could largely be due to overuse of antibiotic agents; 3)UC patients with IPAA have an increased risk for the development of intra-abdominal infections, such as pouch leaks, abscess, and cholangitis from primary sclerosing cholangitis, which require antibiotic therapy with agents similar to the agents used in pouchitis. Bacterial resistance developed from the overuse of antibiotics for pouchitis might jeopardize the treatment of other intra-abdominal infections; 4) overuse of antibiotics can lead to overload of certain commensal bacteria or pathogenic bacteria, leading to pouch inflammation. Therefore, safe and effective agents are needed to treat active pouchitis, particularly on a long-term basis.
AST-120 is manufactured by Kureha Corporation, Japan. The agent was approved in Japan in 1992 for the treatment of patients with chronic kidney disease (CKD). It is comprised of highly adsorptive, porous, spherical carbon particles and is packaged in 2 g sachets for oral administration designed for the treatment of gastrointestinal diseases. AST-120 consists of black microspheres approximately 0.2-0.4 mm in diameter with high adsorption ability and large surface area. Composed mainly of carbon (approximately 96%), the clinical utility of AST-120 is thought to reside in its ability to adsorb low molecular weight toxins, inflammatory mediators, and harmful bile acid products from the gastrointestinal tract, preventing local toxicity and their systemic absorption. AST-120 has a selective adsorption profile for certain acidic and basic organic compounds, and has a significantly lower adsorptive capacity than activated charcoal for digestive enzymes.
This study is an open-label pilot trial in which all patients will receive AST-120 in 2 g sachets three times a day (to be taken between meals at 10:00 am, 3:00 pm, and immediately before going to bed) for 4 complete weeks. AST-120 is a tasteless, odorless, oral preparation. To take the product, patients will tear open the sachets, drop the contents directly on their tongue and wash it down with 8 ounces of water. All antibiotics, probiotics and nutritional agents must have been discontinued for at least 2 weeks prior to study entry. For purposes of this trial response is defined as a > or = 3 point reduction in the 18-point PDAI scoring system. Remission is defined as a PDAI score < 7.
The study population will consist of patients with active pouchitis after ileal pouch-anal anastomosis for Ulcerative Colitis (UC) present with primary symptoms such as increased stool frequency and abdominal pain. The diagnosis of active pouchitis will be defined by a PDAI score > 7 points, with a combined assessment of symptoms, endoscopy, and histology.
An initial cohort of 10 patients will be enrolled. Based on the efficacy outcome (at least 3 out of 10 patients responding) and safety outcome (no significant adverse event associated with study drug) a second cohort of 10 patients will be treated. Patients in the second cohort who are considered responders (i.e., have had at least a 3 point reduction in the 18 point PDAI scoring system) or who are in remission (PDAI<7) are eligible to receive open-label AST-120 for as long as response is maintained up to a maximum of 52 weeks. If, at any time, the patient relapses (PDAI>7 for patients who were in remission, or an increase in PDAI such that at least a 3 point reduction is not maintained for responders), open-label treatment will be discontinued and the patient will be removed from the study. Patients will also discontinue open-label treatment and be removed from the study if warranted by treatment-emergent safety concerns or if, in the opinion of the investigator, it is in the patient's best interest to discontinue the study.
- Conditions
- Pouchitis
- Being tested
- AST-120
- Keywords
- Pouchitis, Active Pouchitis, Safety and Efficacy of AST120
- Medical subject headings
- Pouchitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AST-120Drug
AST-120, 2grams,three times daily for 4 weeks. Responders in the second cohort of patients are eligible to receive AST-120 for up to 52 weeks.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | AST-120, 2grams, three times daily Receives: Drug: AST-120 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Remission induction as defined by a Pouchitis Disease Activity Index (PDAI) score < 7 (Sandborn et al, Mayo Clin Proc 1994), as well as maintenance of remission over 12 months
Measured: 4 weeks induction, 12 months maintenance of remission
Safety: Any adverse events (AEs) deemed possibly, probably, or definitely related to treatment with investigational product
Measured: 4 weeks induction, 12 months maintenance of remission
Secondary outcomes (9)
Response defined as a > or = 3 point reduction in the 18-point PDAI scoring system
Measured: 4 weeks, weeks 28 and 52
Reduction of PDAI clinical symptom score, range from 0 to 6 (e.g., stoll frequency returns to the normal baseline)
Measured: 4 weeks, weeks 28 and 52
Reduction of PDAI endoscopic score, range from 0 to 6
Measured: 4 weeks, weeks 28 and 52
Reduction of PDAI histology score, range from 0 to 6
Measured: 4 weeks, weeks 28 and 52
Need for rescue medication or increased quantity of antidiarrheal medication used during the trial
Measured: 4 weeks, weeks 28 and 52
Quality of Life (Cleveland Global Quality of Life [CGQL] and Short Inflammatory Bowel Disease Questionnaire [SIBDQ]
Measured: 4 weeks, through 52 weeks
Clinical laboratory tests including liver transaminases and alkaline phosphatase
Measured: 4 weeks, through 52 weeks
Worsening GI symptoms (diarrhea, abdominal pain, urgency or bleeding) or new GI and ex-intestinal systemic symptoms (such as headache, nausea, vomiting, and constipation)
Measured: 4 weeks, through 52 weeks
Physical examination, vital signs (blood pressure, heart rate, respiration rate and temperature)
Measured: 4 weeks, through 52 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Dec 2007 (estimated)
- Study startFeb 2007
- Primary completionMar 2008
- Study completionMay 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (40)Papers the sponsor has linked to this study.
- Other trials for PouchitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ocera Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bo Shen, MD, Principal investigator, Clevland Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00583076
- Sponsor's protocol ID
- 06-908
- Status last verified
- Jun 2014
- First submitted
- 20 Dec 2007
- Last updated
- 18 Jun 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Loftus EV Jr, Silverstein MD, Sandborn WJ, Tremaine WJ, Harmsen WS, Zinsmeister AR. Ulcerative colitis in Olmsted County, Minnesota, 1940-1993: incidence, prevalence, and survival. Gut. 2000 Mar;46(3):336-43. doi: 10.1136/gut.46.3.336.
PubMed 10673294Dhillon S; Loftus EV; Tremaine WJ; Jewell DA; Harmsen WS; Zinsmeister AR; Melton LJ; Pemberton H; Wolff BG; Dozois EJ; Cima RR; Larson DW; Sandborn WJ. The natural history of surgery for ulcerative colitis in a population based cohort from Olmsted County, Minnesota. Am J Gastroenterol 2005;100:A819
Gionchetti P, Rizzello F, Helwig U, Venturi A, Lammers KM, Brigidi P, Vitali B, Poggioli G, Miglioli M, Campieri M. Prophylaxis of pouchitis onset with probiotic therapy: a double-blind, placebo-controlled trial. Gastroenterology. 2003 May;124(5):1202-9. doi: 10.1016/s0016-5085(03)00171-9.
PubMed 12730861Penna C, Dozois R, Tremaine W, Sandborn W, LaRusso N, Schleck C, Ilstrup D. Pouchitis after ileal pouch-anal anastomosis for ulcerative colitis occurs with increased frequency in patients with associated primary sclerosing cholangitis. Gut. 1996 Feb;38(2):234-9. doi: 10.1136/gut.38.2.234.
PubMed 8801203Fazio VW, Ziv Y, Church JM, Oakley JR, Lavery IC, Milsom JW, Schroeder TK. Ileal pouch-anal anastomoses complications and function in 1005 patients. Ann Surg. 1995 Aug;222(2):120-7. doi: 10.1097/00000658-199508000-00003.
PubMed 7639579Penna C, Tiret E, Kartheuser A, Hannoun L, Nordlinger B, Parc R. Function of ileal J pouch-anal anastomosis in patients with familial adenomatous polyposis. Br J Surg. 1993 Jun;80(6):765-7. doi: 10.1002/bjs.1800800638.
PubMed 8392425Tjandra JJ, Fazio VW, Church JM, Oakley JR, Milsom JW, Lavery IC. Similar functional results after restorative proctocolectomy in patients with familial adenomatous polyposis and mucosal ulcerative colitis. Am J Surg. 1993 Mar;165(3):322-5. doi: 10.1016/s0002-9610(05)80834-7.
PubMed 8383471Carter MJ, Di Giovine FS, Cox A, Goodfellow P, Jones S, Shorthouse AJ, Duff GW, Lobo AJ. The interleukin 1 receptor antagonist gene allele 2 as a predictor of pouchitis following colectomy and IPAA in ulcerative colitis. Gastroenterology. 2001 Oct;121(4):805-11. doi: 10.1053/gast.2001.28017.
PubMed 11606494Brett PM, Yasuda N, Yiannakou JY, Herbst F, Ellis HJ, Vaughan R, Nicholls RJ, Ciclitira PJ. Genetic and immunological markers in pouchitis. Eur J Gastroenterol Hepatol. 1996 Oct;8(10):951-5. doi: 10.1097/00042737-199610000-00003.
PubMed 8930557Meier CB, Hegazi RA, Aisenberg J, Legnani PE, Nilubol N, Cobrin GM, Duerr RH, Gorfine SR, Bauer JJ, Sachar DB, Plevy SE. Innate immune receptor genetic polymorphisms in pouchitis: is CARD15 a susceptibility factor? Inflamm Bowel Dis. 2005 Nov;11(11):965-71. doi: 10.1097/01.mib.0000186407.25694.cf.
PubMed 16239841Sandborn WJ. Pouchitis following ileal pouch-anal anastomosis: definition, pathogenesis, and treatment. Gastroenterology. 1994 Dec;107(6):1856-60. doi: 10.1016/0016-5085(94)90832-x. No abstract available.
PubMed 7958702Duffy M, O'Mahony L, Coffey JC, Collins JK, Shanahan F, Redmond HP, Kirwan WO. Sulfate-reducing bacteria colonize pouches formed for ulcerative colitis but not for familial adenomatous polyposis. Dis Colon Rectum. 2002 Mar;45(3):384-8. doi: 10.1007/s10350-004-6187-z.
PubMed 12068199Nasmyth DG, Godwin PG, Dixon MF, Williams NS, Johnston D. Ileal ecology after pouch-anal anastomosis or ileostomy. A study of mucosal morphology, fecal bacteriology, fecal volatile fatty acids, and their interrelationship. Gastroenterology. 1989 Mar;96(3):817-24.
PubMed 2914643Gosselink MP, Schouten WR, van Lieshout LM, Hop WC, Laman JD, Ruseler-van Embden JG. Eradication of pathogenic bacteria and restoration of normal pouch flora: comparison of metronidazole and ciprofloxacin in the treatment of pouchitis. Dis Colon Rectum. 2004 Sep;47(9):1519-25. doi: 10.1007/s10350-004-0623-y. Epub 2004 Jul 8.
PubMed 15486751Shen B, Achkar JP, Lashner BA, Ormsby AH, Remzi FH, Brzezinski A, Bevins CL, Bambrick ML, Seidner DL, Fazio VW. A randomized clinical trial of ciprofloxacin and metronidazole to treat acute pouchitis. Inflamm Bowel Dis. 2001 Nov;7(4):301-5. doi: 10.1097/00054725-200111000-00004.
PubMed 11720319
Study at a glance
From the registry record, last updated by the sponsor on 18 Jun 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of the Safety and Efficacy of AST-120 in the Treatment of Active Pouchitis
- ClinicalTrials.gov ID
- NCT00583076
- Acronym / sponsor ID
- 06-908
- Conditions
- Pouchitis
- Keywords
- Pouchitis, Active Pouchitis, Safety and Efficacy of AST120
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Ocera TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- Feb 2007
- Primary completion
- Mar 2008 (actual)
- Study completion
- May 2008 (actual)
- First posted
- 31 Dec 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of the study is to assess the safety and efficacy of an investigational agent, AST-120, in treating patients with active pouchitis. This is an open-label trial which means that all patients will receive AST-120 in 2g sachets (packets)three times a day for 4 weeks. All antibiotics, probiotics and nutritional agents must have been discontinued for at least 2 weeks prior to study entry. An initial group of 10 patients will be enrolled. If there are no serious adverse events associated with the study drug and at least 3 of the 10 patients respond, a second group of 10 patients will be enrolled. In the second group of patients, those patients who are considered responders or who are in remission are eligible to receive open-label AST-120 for as long as response is maintained up to a maximum of 52 weeks. Patients will have clinic visits at the start of the study and at week 4. If continuing on open label AST-120 after week 4, patients will have clinic visits every 12 weeks to assess the continuing safety and efficacy of AST-120. Endoscopies will be performed at the start of the study, week 4, week 28, week 52 or early termination.
Detailed description
The management and prognosis vary in different types of pouchitis. For antibiotic-responsive pouchitis, the first-line therapy includes a 2-week course of metronidazole or ciprofloxacin. A relapsing course of pouchitis is common. Of the patients with acute pouchitis, 61% would develop at least one recurrence. Typically, patient's symptoms and endoscopic and histologic inflammation respond favorably to antibiotic therapy, but symptoms quickly recur when antibiotics are discontinued. This group of patients is classified as having antibiotic-dependent pouchitis and often requires long-term antibiotic or probiotic therapy to keep the disease in remission.
Although the majority of patients with active pouchitis respond favorably to antibiotic therapy, relapse is common, which often requires frequent antibiotic therapy. The concerns about frequent use of antibiotic agents are: 1)antibiotics such as metronidazole often cause adverse effects; 2)long-term or frequent use of antibiotics, including ciprofloxacin, metronidazole, and rifaximin, often leads to bacterial resistance. In clinical practice, we have encountered more and more patients with antibiotic-refractory pouchitis, which could largely be due to overuse of antibiotic agents; 3)UC patients with IPAA have an increased risk for the development of intra-abdominal infections, such as pouch leaks, abscess, and cholangitis from primary sclerosing cholangitis, which require antibiotic therapy with agents similar to the agents used in pouchitis. Bacterial resistance developed from the overuse of antibiotics for pouchitis might jeopardize the treatment of other intra-abdominal infections; 4) overuse of antibiotics can lead to overload of certain commensal bacteria or pathogenic bacteria, leading to pouch inflammation. Therefore, safe and effective agents are needed to treat active pouchitis, particularly on a long-term basis.
AST-120 is manufactured by Kureha Corporation, Japan. The agent was approved in Japan in 1992 for the treatment of patients with chronic kidney disease (CKD). It is comprised of highly adsorptive, porous, spherical carbon particles and is packaged in 2 g sachets for oral administration designed for the treatment of gastrointestinal diseases. AST-120 consists of black microspheres approximately 0.2-0.4 mm in diameter with high adsorption ability and large surface area. Composed mainly of carbon (approximately 96%), the clinical utility of AST-120 is thought to reside in its ability to adsorb low molecular weight toxins, inflammatory mediators, and harmful bile acid products from the gastrointestinal tract, preventing local toxicity and their systemic absorption. AST-120 has a selective adsorption profile for certain acidic and basic organic compounds, and has a significantly lower adsorptive capacity than activated charcoal for digestive enzymes.
This study is an open-label pilot trial in which all patients will receive AST-120 in 2 g sachets three times a day (to be taken between meals at 10:00 am, 3:00 pm, and immediately before going to bed) for 4 complete weeks. AST-120 is a tasteless, odorless, oral preparation. To take the product, patients will tear open the sachets, drop the contents directly on their tongue and wash it down with 8 ounces of water. All antibiotics, probiotics and nutritional agents must have been discontinued for at least 2 weeks prior to study entry. For purposes of this trial response is defined as a > or = 3 point reduction in the 18-point PDAI scoring system. Remission is defined as a PDAI score < 7.
The study population will consist of patients with active pouchitis after ileal pouch-anal anastomosis for Ulcerative Colitis (UC) present with primary symptoms such as increased stool frequency and abdominal pain. The diagnosis of active pouchitis will be defined by a PDAI score > 7 points, with a combined assessment of symptoms, endoscopy, and histology.
An initial cohort of 10 patients will be enrolled. Based on the efficacy outcome (at least 3 out of 10 patients responding) and safety outcome (no significant adverse event associated with study drug) a second cohort of 10 patients will be treated. Patients in the second cohort who are considered responders (i.e., have had at least a 3 point reduction in the 18 point PDAI scoring system) or who are in remission (PDAI<7) are eligible to receive open-label AST-120 for as long as response is maintained up to a maximum of 52 weeks. If, at any time, the patient relapses (PDAI>7 for patients who were in remission, or an increase in PDAI such that at least a 3 point reduction is not maintained for responders), open-label treatment will be discontinued and the patient will be removed from the study. Patients will also discontinue open-label treatment and be removed from the study if warranted by treatment-emergent safety concerns or if, in the opinion of the investigator, it is in the patient's best interest to discontinue the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: AST-120AST-120, 2grams, three times daily |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Patients with a current episode of active pouchitis (defined as having a PDAI score > 7) after IPAA for UC confirmed by endoscopy and histology
- Patients with active pouchitis who have never been treated with antibiotics (antibiotic-naive) or who have been previously treated with antibiotics and responded. Antibiotic-dependent patients may be enrolled as long as antibiotic use is discontinued for at least two weeks prior to study entry. Antibiotic-dependent pouchitis is defined as a condition in which a patient with frequent episodes (> or = 4 episodes per year) of pouchitis or persistent symptoms requires long-term, continuous antibiotic or probiotic therapy to keep the disease in remission.
- Able to give informed consent
- Able and willing to comply with all study procedures
- Females must be post-menopausal, surgically incapable of bearing children, or practicing a reliable single barrier method of birth control (condom, intrauterine devices, spermicide and barrier, Depot). Partner/spouse sterility may also qualify at the investigator's discretion. Females of child-bearing potential must have a negative urine pregnancy test at baseline. Oral contraceptives are not acceptable as there is a potential interaction with AST-120.
Key exclusion criteria (21 listed)
- Patients previously treated with infliximab or any investigational immunosuppressant/immunomodulator
- Patients whose condition is severe enough that, in the investigator's opinion, withholding antibiotics for 4 weeks during the AST-120 trial is not feasible
- Patients undergoing chemotherapy for the treatment of cancer
- Antibiotic use within 2 weeks prior to the entry of the study
- Crohn's disease of the pouch, including inflammatory, fibrostenotic, or fistulizing phenotypes, based on the previously established diagnostic criteria (Shen B, et al. Am J Gastroenterol 2006 in press)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AST-120AST-120, 2grams,three times daily for 4 weeks. Responders in the second cohort of patients are eligible to receive AST-120 for up to 52 weeks. | Drug | 1 |
Primary outcome
Remission induction as defined by a Pouchitis Disease Activity Index (PDAI) score < 7 (Sandborn et al, Mayo Clin Proc 1994), as well as maintenance of remission over 12 months
Time frame: 4 weeks induction, 12 months maintenance of remission
Safety: Any adverse events (AEs) deemed possibly, probably, or definitely related to treatment with investigational product
Time frame: 4 weeks induction, 12 months maintenance of remission
9 secondary outcomes
Response defined as a > or = 3 point reduction in the 18-point PDAI scoring system
Time frame: 4 weeks, weeks 28 and 52
Reduction of PDAI clinical symptom score, range from 0 to 6 (e.g., stoll frequency returns to the normal baseline)
Time frame: 4 weeks, weeks 28 and 52
Reduction of PDAI endoscopic score, range from 0 to 6
Time frame: 4 weeks, weeks 28 and 52
Reduction of PDAI histology score, range from 0 to 6
Time frame: 4 weeks, weeks 28 and 52
Need for rescue medication or increased quantity of antidiarrheal medication used during the trial
Time frame: 4 weeks, weeks 28 and 52
Quality of Life (Cleveland Global Quality of Life [CGQL] and Short Inflammatory Bowel Disease Questionnaire [SIBDQ]
Time frame: 4 weeks, through 52 weeks
Clinical laboratory tests including liver transaminases and alkaline phosphatase
Time frame: 4 weeks, through 52 weeks
Worsening GI symptoms (diarrhea, abdominal pain, urgency or bleeding) or new GI and ex-intestinal systemic symptoms (such as headache, nausea, vomiting, and constipation)
Time frame: 4 weeks, through 52 weeks
Physical examination, vital signs (blood pressure, heart rate, respiration rate and temperature)
Time frame: 4 weeks, through 52 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jun 2014.
- Background: PubMed 10673294Loftus EV Jr, Silverstein MD, Sandborn WJ, Tremaine WJ, Harmsen WS, Zinsmeister AR. Ulcerative colitis in Olmsted County, Minnesota, 1940-1993: incidence, prevalence, and survival. Gut. 2000 Mar;46(3):336-43. doi: 10.1136/gut.46.3.336.
- BackgroundDhillon S; Loftus EV; Tremaine WJ; Jewell DA; Harmsen WS; Zinsmeister AR; Melton LJ; Pemberton H; Wolff BG; Dozois EJ; Cima RR; Larson DW; Sandborn WJ. The natural history of surgery for ulcerative colitis in a population based cohort from Olmsted County, Minnesota. Am J Gastroenterol 2005;100:A819
- Background: PubMed 12730861Gionchetti P, Rizzello F, Helwig U, Venturi A, Lammers KM, Brigidi P, Vitali B, Poggioli G, Miglioli M, Campieri M. Prophylaxis of pouchitis onset with probiotic therapy: a double-blind, placebo-controlled trial. Gastroenterology. 2003 May;124(5):1202-9. doi: 10.1016/s0016-5085(03)00171-9.
- Background: PubMed 8801203Penna C, Dozois R, Tremaine W, Sandborn W, LaRusso N, Schleck C, Ilstrup D. Pouchitis after ileal pouch-anal anastomosis for ulcerative colitis occurs with increased frequency in patients with associated primary sclerosing cholangitis. Gut. 1996 Feb;38(2):234-9. doi: 10.1136/gut.38.2.234.
- Background: PubMed 7639579Fazio VW, Ziv Y, Church JM, Oakley JR, Lavery IC, Milsom JW, Schroeder TK. Ileal pouch-anal anastomoses complications and function in 1005 patients. Ann Surg. 1995 Aug;222(2):120-7. doi: 10.1097/00000658-199508000-00003.
- Background: PubMed 8392425Penna C, Tiret E, Kartheuser A, Hannoun L, Nordlinger B, Parc R. Function of ileal J pouch-anal anastomosis in patients with familial adenomatous polyposis. Br J Surg. 1993 Jun;80(6):765-7. doi: 10.1002/bjs.1800800638.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bo Shen, MD principal investigator
Clevland Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing AST-120 in people with Pouchitis, run by Ocera Therapeutics at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Jun 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Remission induction as defined by a Pouchitis Disease Activity Index (PDAI) score < 7 (Sandborn et al, Mayo Clin Proc 1994), as well as maintenance of remission over 12 months (time frame: 4 weeks induction, 12 months maintenance of remission). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00583076, which also lists 40 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jun 2014.