Ignite Creation Date:
2024-05-05 @ 11:55 AM
Last Modification Date:
2024-10-26 @ 9:16 AM
Study NCT ID:
NCT00177775
Status:
TERMINATED
Last Update Posted:
2008-12-17
First Post:
2005-09-13
Brief Title:
Whey Protein Concentrate 40 Made of Milk of Immunized Cows to Aid in the Prevention of Relapse of Clostridium Difficile-Diarrhea
Sponsor:
University of Pittsburgh
Organization:
University of Pittsburgh
Study Overview
Official Title:
Whey Protein Concentrate 40 WPC-40 Made of Milk of Immunized Cows to Aid in the Prevention of Relapse of Clostridium Difficile-Diarrhea A Prospective Randomized Controlled Phase II Study - Version 51B
Status:
TERMINATED
Status Verified Date:
2008-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Study is completed and analysis completed
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The primary objective of this study is to assess the safety of the investigational agent MucoMilk a polyclonal-antibody enriched Whey Protein Concentrate 40 WPC-40 made of milk of immunized cows Secondary objectives will investigate the effectiveness of MucoMilk as an aid in the prevention of relapse of C difficile-associated diarrhea CDAD
Detailed Description:
This is a single-center prospective controlled randomized open-label study Sixty subjects will be randomized 21 to receive MucoMilk n40 or to the control arm with no specific product intervention n20 There is no effective FDA-approved treatment to prevent recurrence of CDAD that is being withheld from subjects who will be randomized to the control arm
The sponsor will prepare sequentially numbered batches of MucoMilk for the entire 2-week dosing period or 42 packets and will prepare a randomization table that will be held in confidence by the University of Pittsburgh Investigational Drug Service IDS pharmacist Each subject will be assigned a sequential study number ie 1 2 3 etc as they are enrolled in the study Upon enrollment research staff will contact the IDS pharmacist to obtain the subjects study number and randomization assignment MucoMilk or no specific product intervention Research staff will not have access to the randomization table
Subjects assigned to receive MucoMilk will be given a box containing 14 leaflets numbered Day 1 to Day 14 Each leaflet consists of 3 packets labeled morning noon and evening connected by perforated paper Subjects will be provided with one box and instructed not to alter their diet during the two-week course
At the University of Pittsburgh it is anticipated that up to 150 subjects will need to be screened in order to enter 60 subjects on study Subjects may participate in this study for up to 63 days
Subjects will be managed and followed per institutional infection control guidelines for C difficile containment regardless of assigned study group Subjects will receive appropriate treatment for comorbid conditions based on the judgement of the treating physician and practice guidelines With the exception of investigational agents any clinically indicated concomitant medications for symptomatic relief or support will be allowed upon recommendation and approval of the investigator
For this trial the safety of MucoMilk will be determined by passive self-reporting in a subject diary and active surveillance by preset interview of any adverse events In addition a physical exam and extensive hematologic and biochemical testing will be performed before and after MucoMilk administration
Efficacy will be examined by assessing CDAD relapse rates A relapse of CDAD will be reached when in comparison with the day before stools have become looser and either 1 the frequency of stools has increased for 2 consecutive days or 2 on a single day the frequency increases by 3 stools or 3 occurrence of 6 stoolsday on any day In this respect CDAD relapse will be defined as probable if occurring as described for the first 18 days following MucoMilk initiation with a negative C diff toxin assay or proven if occurring at any time with a positive C diff toxin assay A subject will be considered a treatment failure if she meets the above criteria for a CDAD relapse
Subjects who cannot or will not be included in this study will be asked to be followed for 60 days off-study for any adverse reactions or CDAD relapses per subject diary documentation These subjects may receive treatment for CDAD outside of this study as standard of care but will not be offered any study product or intervention through randomization
33 Clinical and Laboratory Evaluations Subjects may be either inpatients or outpatients during their participation in this study Inpatient study visits will take place at UPMC Presbyterian UPMC Montefiore or UPMC Shadyside Outpatient study visits will take place at the Infectious Disease Clinic in the Falk Medical Building Each study visit will last about one hour depending on the procedures to be done at that visit
All procedures performed in this study are research-required with the exception of the antibiotic treatment for CDAD initiated at the Diagnosis Visit and any stool toxin assays performed to confirm suspected CDAD relapse as these are both standard of care for CDAD The investigator will review the results of all evaluations and these results will become part of the subjects research record
It may be necessary for the subject to make additional visits during participation in this study to have any of the study procedures listed below repeated in the event of unforeseen or unanticipated abnormal results difficulties in sample shipping processing or testing andor if the subject experiences any changes in hisher physical condition
Screening Procedures
Screening Visit for all subjects will occur within 3 days prior to Day 1 or will be combined with the Day 1 Visit as subjects may be randomized if currently receiving or have completed standard antibiotic therapy for CDAD Subjects will be asked to read and sign the informed consent before any study procedures are performed Evaluations to be done at this visit include
Complete physical examination
Collection of demographic data medication history chronic health score and primaryrelapse CDAD episode information
Female subjects of childbearing potential will be given a urine pregnancy test which must be negative
Subjects currently on a standard antibiotic course for CDAD with oralintravenous metronidazole andor vancomycin will continue this therapy for a minimum of 10 days per standard of care at the discretion of the study physician
Experimental Procedures
Day 1 Visit will occur during or within 3 days after Screening If diarrhea has recurred and CDAD relapse is suspected stool sample for toxin assay by ELISAcell test culture and microscopy If positive for CDAD the subject will be taken off study and followed as per standard of care for CDAD relapse Evaluations include
Karnofsky and EORTC GI scores
45ml blood draw for hematology Hgb WBC wdiff platelets renal function creatinine urea electrolytes liver function ALT AST alkaline phosphatase albumin glucose total protein bilirubin lipids IgE and for storage
Female subjects of childbearing potential will be given a urine pregnancy test which must be negative
Distribution of subject diary for recording of any adverse events and the number and consistency of all stools
At the completion of these evaluations MucoMilk subjects will receive enough study product for entire 14-day dosing period be counseled on proper storage and administration by the study staff and be given a study agent diary to record compliance
Day 7 to 9 Visit will be conducted by telephone for outpatients or by visit for inpatients to review stool frequency and consistency and any perceived adverse events from MucoMilk if applicable If a CDAD relapse is suspected based on this review the subject will be asked to provide a stool sample for toxin assay If positive for CDAD the subject will be taken off MucoMilk if applicable off study and followed as per standard of care for CDAD relapse
Follow-Up Procedures
Day 18 to 21 Visit evaluations include
Targeted physical exam
Karnofsky and EORTC GI scores
45ml blood draw for hematology renal and liver function tests lipids IgE and for storage
If diarrhea has recurred and CDAD relapse is suspected stool sample for toxin assay by ELISAcell test culture and microscopy
Collection of any unused investigational product and study agent diary
Subject diary review Subjects will continue to record any adverse events and the number and consistency of all stools during the follow-up period
Through Day 60 weekly visits will be conducted by telephone or visit to review bowel movements and stool consistency If a CDAD relapse is suspected based on any review the subject will be asked to provide a stool sample for toxin assay If positive for CDAD the subject will be taken off study and followed as per standard of care for CDAD relapse The occurrence and time to the occurrence of any new relapse in this period will be evaluated as well Subjects who complete the study through Day 60 with no relapse of CDAD will be asked to return their diary discharged from study participation and referred back to their primary care physician for follow-up
34 Storage of Biological Samples During this study serum samples collected on Day 1 and on Day 18 to 21 will be labeled with the subjects study identification number and date collected processed frozen and stored at MucoVax for future testing that is part of this study including investigation of antibodies directed against C difficile and its toxins Also the presence of human antibodies directed against bovine immunoglobulins may be examined The sponsor will have sole control over these samples which will be stored for an indefinite period of time Subjects will not be notified of the results of these future studies as the information collected will not apply to the management of their disease at the time these tests are done If these samples are provided to secondary investigators these samples devoid of all subject identifiers and rendered anonymous will be obtained from the sponsor by the secondary investigator The secondary investigator will not have direct access to any subject identifiers or related subject information
The sponsor will prepare sequentially numbered batches of MucoMilk for the entire 2-week dosing period or 42 packets and will prepare a randomization table that will be held in confidence by the University of Pittsburgh Investigational Drug Service IDS pharmacist Each subject will be assigned a sequential study number ie 1 2 3 etc as they are enrolled in the study Upon enrollment research staff will contact the IDS pharmacist to obtain the subjects study number and randomization assignment MucoMilk or no specific product intervention Research staff will not have access to the randomization table
Subjects assigned to receive MucoMilk will be given a box containing 14 leaflets numbered Day 1 to Day 14 Each leaflet consists of 3 packets labeled morning noon and evening connected by perforated paper Subjects will be provided with one box and instructed not to alter their diet during the two-week course
At the University of Pittsburgh it is anticipated that up to 150 subjects will need to be screened in order to enter 60 subjects on study Subjects may participate in this study for up to 63 days
Subjects will be managed and followed per institutional infection control guidelines for C difficile containment regardless of assigned study group Subjects will receive appropriate treatment for comorbid conditions based on the judgement of the treating physician and practice guidelines With the exception of investigational agents any clinically indicated concomitant medications for symptomatic relief or support will be allowed upon recommendation and approval of the investigator
For this trial the safety of MucoMilk will be determined by passive self-reporting in a subject diary and active surveillance by preset interview of any adverse events In addition a physical exam and extensive hematologic and biochemical testing will be performed before and after MucoMilk administration
Efficacy will be examined by assessing CDAD relapse rates A relapse of CDAD will be reached when in comparison with the day before stools have become looser and either 1 the frequency of stools has increased for 2 consecutive days or 2 on a single day the frequency increases by 3 stools or 3 occurrence of 6 stoolsday on any day In this respect CDAD relapse will be defined as probable if occurring as described for the first 18 days following MucoMilk initiation with a negative C diff toxin assay or proven if occurring at any time with a positive C diff toxin assay A subject will be considered a treatment failure if she meets the above criteria for a CDAD relapse
Subjects who cannot or will not be included in this study will be asked to be followed for 60 days off-study for any adverse reactions or CDAD relapses per subject diary documentation These subjects may receive treatment for CDAD outside of this study as standard of care but will not be offered any study product or intervention through randomization
33 Clinical and Laboratory Evaluations Subjects may be either inpatients or outpatients during their participation in this study Inpatient study visits will take place at UPMC Presbyterian UPMC Montefiore or UPMC Shadyside Outpatient study visits will take place at the Infectious Disease Clinic in the Falk Medical Building Each study visit will last about one hour depending on the procedures to be done at that visit
All procedures performed in this study are research-required with the exception of the antibiotic treatment for CDAD initiated at the Diagnosis Visit and any stool toxin assays performed to confirm suspected CDAD relapse as these are both standard of care for CDAD The investigator will review the results of all evaluations and these results will become part of the subjects research record
It may be necessary for the subject to make additional visits during participation in this study to have any of the study procedures listed below repeated in the event of unforeseen or unanticipated abnormal results difficulties in sample shipping processing or testing andor if the subject experiences any changes in hisher physical condition
Screening Procedures
Screening Visit for all subjects will occur within 3 days prior to Day 1 or will be combined with the Day 1 Visit as subjects may be randomized if currently receiving or have completed standard antibiotic therapy for CDAD Subjects will be asked to read and sign the informed consent before any study procedures are performed Evaluations to be done at this visit include
Complete physical examination
Collection of demographic data medication history chronic health score and primaryrelapse CDAD episode information
Female subjects of childbearing potential will be given a urine pregnancy test which must be negative
Subjects currently on a standard antibiotic course for CDAD with oralintravenous metronidazole andor vancomycin will continue this therapy for a minimum of 10 days per standard of care at the discretion of the study physician
Experimental Procedures
Day 1 Visit will occur during or within 3 days after Screening If diarrhea has recurred and CDAD relapse is suspected stool sample for toxin assay by ELISAcell test culture and microscopy If positive for CDAD the subject will be taken off study and followed as per standard of care for CDAD relapse Evaluations include
Karnofsky and EORTC GI scores
45ml blood draw for hematology Hgb WBC wdiff platelets renal function creatinine urea electrolytes liver function ALT AST alkaline phosphatase albumin glucose total protein bilirubin lipids IgE and for storage
Female subjects of childbearing potential will be given a urine pregnancy test which must be negative
Distribution of subject diary for recording of any adverse events and the number and consistency of all stools
At the completion of these evaluations MucoMilk subjects will receive enough study product for entire 14-day dosing period be counseled on proper storage and administration by the study staff and be given a study agent diary to record compliance
Day 7 to 9 Visit will be conducted by telephone for outpatients or by visit for inpatients to review stool frequency and consistency and any perceived adverse events from MucoMilk if applicable If a CDAD relapse is suspected based on this review the subject will be asked to provide a stool sample for toxin assay If positive for CDAD the subject will be taken off MucoMilk if applicable off study and followed as per standard of care for CDAD relapse
Follow-Up Procedures
Day 18 to 21 Visit evaluations include
Targeted physical exam
Karnofsky and EORTC GI scores
45ml blood draw for hematology renal and liver function tests lipids IgE and for storage
If diarrhea has recurred and CDAD relapse is suspected stool sample for toxin assay by ELISAcell test culture and microscopy
Collection of any unused investigational product and study agent diary
Subject diary review Subjects will continue to record any adverse events and the number and consistency of all stools during the follow-up period
Through Day 60 weekly visits will be conducted by telephone or visit to review bowel movements and stool consistency If a CDAD relapse is suspected based on any review the subject will be asked to provide a stool sample for toxin assay If positive for CDAD the subject will be taken off study and followed as per standard of care for CDAD relapse The occurrence and time to the occurrence of any new relapse in this period will be evaluated as well Subjects who complete the study through Day 60 with no relapse of CDAD will be asked to return their diary discharged from study participation and referred back to their primary care physician for follow-up
34 Storage of Biological Samples During this study serum samples collected on Day 1 and on Day 18 to 21 will be labeled with the subjects study identification number and date collected processed frozen and stored at MucoVax for future testing that is part of this study including investigation of antibodies directed against C difficile and its toxins Also the presence of human antibodies directed against bovine immunoglobulins may be examined The sponsor will have sole control over these samples which will be stored for an indefinite period of time Subjects will not be notified of the results of these future studies as the information collected will not apply to the management of their disease at the time these tests are done If these samples are provided to secondary investigators these samples devoid of all subject identifiers and rendered anonymous will be obtained from the sponsor by the secondary investigator The secondary investigator will not have direct access to any subject identifiers or related subject information
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