Small Bowel Capsule Endoscopy Findings in Patients Receiving Cellcept®

• Sponsor: University of California, Los Angeles (Other)
• Overall Status: Completed
• CT.gov ID: NCT00652834
• Collaborator: Novartis (Industry)
• Enrollment: 23
• Location: 1
• Arm: 1
• Duration (Months): 25
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

The purpose of this study is to learn more about symptoms and gastrointestinal lesions associated with taking myfortic® by switching patients to a delayed release formulation that is developed to alleviate GI symptoms. A comparison of the frequency and severity of GI symptoms observed in patients treated with MMF (cellcept®) after conversion to myfortic® will be measured by using a self-assessed questionnaire called Gastrointestinal Symptom Rating Scale (GSRS). To prove the incidence and improvement of GI lesions in patients treated with MMF (cellcept®) after conversion to myfortic® will be measured by using Small Bowel Capsule Endoscopy (SBCE).

Condition or Disease	Intervention/Treatment	Phase
Gastrointestinal Lesions; Signs and Symptoms, Digestive	Procedure: Small bowel capsule endoscopy (SBCE); Drug: myfortic	Phase 4

Detailed Description

Myfortic® recently introduced to the market has shown to be similar to MMF in how effectively it works and how well it is tolerated. Both drugs have the same active ingredient, but they are different in the way that they deliver them to the body. Myfortic® is an advanced, enteric coated formulation of mycophenolate sodium (EC-MPS) that delays the release of the active ingredient, MPA. MPA has more potent effects on the lymphocytes than other cells. This makes for improved GI tolerability of the MPA therapy.

Study Design

• Study Type: Interventional
• Actual Enrollment: 23 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Gastrointestinal Mucosal Findings in Patients Receiving Mycophenolic Acid (MPA) as Demonstrated by Small Bowel Capsule Endoscopy (SBCE)
• Study Start Date: Apr 1, 2009
• Actual Primary Completion Date: Mar 1, 2011
• Actual Study Completion Date: May 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Other: kidney recipients with GI symptoms This was a four-week study designed to investigate GI mucosal lesions by SBCE in kidney transplant recipients who were using MMF, and to examine the changes in clinical symptoms and intestinal mucosa lesions 30 days after switching over from MMF to EC-MPS. The patient was switched from MMF to EC-MPS (Myfortic) on the equimola basis.	Procedure: Small bowel capsule endoscopy (SBCE); SBCE will be performed at Day 2 and Day 30.; Other Names: PillCamEso ; Drug: myfortic; switching from mycophenolate mofetil to mycophenolic acid on equimolar basis; Other Names: EC-MPS

Outcome Measures

Primary Outcome Measures

1. GI Mucosal Lesions Change and Clinical Symptoms Using The Gastrointestinal Symptom Rating Scale (GSRS) Score [one month]

   The GSRS has a seven-point graded Likert-type scale where 1 represents absence of troublesome symptoms and 7 represents very troublesome symptoms. A higher GSRS indicate worse symptoms and a difference between D30 and last SBCE scores greater or equal to 0.3 can be considered as a clinically significant improvement in the symptoms.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female patients between 18 and 75 years of age.

• Recipients of first or second cadaveric, living unrelated or living related kidney transplant.

• Recipients who are at least 4 weeks post renal transplantation with stable renal function.

• Patients who have used MMF at least 10 days and are currently receiving MMF. (up to 3g/day dosage allowed)

• Patients with at least one moderate or severe upper or lower GI complaints.

• Patients' immunosuppressive regimen other than steroids as well as medication for treatment of GI symptoms must be unchanged for at least 1 week prior to study start.

• Females of childbearing potential must have a negative pregnancy test prior to the inclusion period. Effective contraception must be used during the trial, and for 4 weeks following discontinuation of the study medication.

• Patients who are willing and able to participate in the full course of the study and from whom written informed consent has been obtained.

Exclusion Criteria:

• Multi-organ transplant patients or previous transplant with any other organ different from kidney.

• The presence of a severe GI disorder. History of a significant GI disorder prior to transplant that has remained unchanged since transplant and/or the introduction of MMF will exclude patient.

• Evidence of any GI disorder induced by an infection, underlying medical condition, or concomitant medication other than MMF.

• Modification of GI medication or MMF dose within last 1 week.

• Evidence of graft rejection, treatment of acute rejection, or unstable renal function within 4 weeks prior to the Baseline visit.

• Patients who have received an investigational immunosuppressive drug within 4 weeks prior to study entry.

• Patients with a history of malignancy within the last five years, except excised squamous or basal cell carcinoma of the skin.

• Pregnant or nursing women.

• Patients with thrombocytopenia (<75,000/mm3), with an absolute neutrophil count of <1,500/mm3 and/or leukocytopenia (<3,500/mm3), and/or hemoglobin <9.0 g/dL prior to enrollment.

• Presence of clinically significant pyrexia and/or infection requiring continued therapy.

• Evidence of severe liver disease [incl. abnormal liver profile i.e. AST, ALT or total bilirubin = 3 times the upper limit of normal].

• Patients who have any anatomical GI tract defects which have risk of capsule getting stuck such as tumor or previous abdominal surgery.

• Abnormal physical or laboratory findings of clinical significance within 2 weeks of inclusion which would interfere with the objectives of the study.

• Patients with symptoms of significant illness or evidence of current drug and/or alcohol abuse.

• Inability to self-administer the GSRS & OTE questionnaire.

• Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer.

• History of hypersensitivity to any of the study drugs or to drugs with similar chemical structures.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California, Los Angeles	Los Angeles	California	United States	90095

Sponsors and Collaborators

• University of California, Los Angeles
• Novartis

Investigators

• Principal Investigator: suphamai bunnapradist, MD, University of California, Los Angeles

Study Documents (Full-Text)

None provided.

More Information

Publications

• Behrend M. Adverse gastrointestinal effects of mycophenolate mofetil: aetiology, incidence and management. Drug Saf. 2001;24(9):645-63. Review.
• Dimenäs E, Carlsson G, Glise H, Israelsson B, Wiklund I. Relevance of norm values as part of the documentation of quality of life instruments for use in upper gastrointestinal disease. Scand J Gastroenterol Suppl. 1996;221:8-13.
• Kleinman L, Faull R, Walker R, Ramesh Prasad GV, Ambuehl P, Bahner U. Gastrointestinal-specific patient-reported outcome instruments differentiate between renal transplant patients with or without GI complications. Transplant Proc. 2005 Mar;37(2):846-9.
• Meier-Kriesche HU, Steffen BJ, Hochberg AM, Gordon RD, Liebman MN, Morris JA, Kaplan B. Long-term use of mycophenolate mofetil is associated with a reduction in the incidence and risk of late rejection. Am J Transplant. 2003 Jan;3(1):68-73.
• Ojo AO, Meier-Kriesche HU, Hanson JA, Leichtman AB, Cibrik D, Magee JC, Wolfe RA, Agodoa LY, Kaplan B. Mycophenolate mofetil reduces late renal allograft loss independent of acute rejection. Transplantation. 2000 Jun 15;69(11):2405-9.
• Salvadori M, Holzer H, de Mattos A, Sollinger H, Arns W, Oppenheimer F, Maca J, Hall M; ERL B301 Study Groups. Enteric-coated mycophenolate sodium is therapeutically equivalent to mycophenolate mofetil in de novo renal transplant patients. Am J Transplant. 2004 Feb;4(2):231-6.
• Shaw LM, Sollinger HW, Halloran P, Morris RE, Yatscoff RW, Ransom J, Tsina I, Keown P, Holt DW, Lieberman R, et al. Mycophenolate mofetil: a report of the consensus panel. Ther Drug Monit. 1995 Dec;17(6):690-9. Review.

• Responsible Party: Suphamai Bunnapradist, Principal Investigator, University of California, Los Angeles
• ClinicalTrials.gov Identifier: NCT00652834
• Other Study ID Numbers: 11-001911
• First Posted: Apr 4, 2008
• Last Update Posted: Mar 4, 2016
• Last Verified: Dec 1, 2014

• Keywords provided by Suphamai Bunnapradist, Principal Investigator, University of California, Los Angeles: Renal transplant recipients; Gastrointestinal findings in small bowel capsule endoscopy; Mycophenolic acid; Mycophenolate Mofetil; Mycophenolate Sodium
• Additional relevant MeSH terms: Signs and Symptoms, Digestive; Mycophenolic Acid

Study Results

Participant Flow

Recruitment Details	Kidney Transplant Clinic

Arm/Group Title	Kidney Transplant Recipients With GI Symptoms
Arm/Group Description	Small bowel capsule endoscopy (SBCE): SBCE will be performed at Day 2 and Day 30. Small bowel capsule endoscopy (SBCE): SBCE will be performed at Day 2.
Period Title: Overall Study
STARTED	23
COMPLETED	18
NOT COMPLETED	5

Baseline Characteristics

Arm/Group Title	Kidney Transplant Recipients With GI Symptoms
Arm/Group Description	If there are negative findings on SBCE, that will be continued on MMF. No need to have second SBCE. Small bowel capsule endoscopy (SBCE): SBCE will be performed at Day 2 and Day 30. Small bowel capsule endoscopy (SBCE): SBCE will be performed at Day 2.
Overall Participants	18
Age (years) [Median (Standard Deviation) ]
Median (Standard Deviation) [years]	45 (11.69)
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	17 94.4%
>=65 years	1 5.6%
Sex: Female, Male (Count of Participants)
Female	8 44.4%
Male	10 55.6%
Region of Enrollment (participants) [Number]
United States	18 100%

Outcome Measures

1. Primary Outcome

Title	GI Mucosal Lesions Change and Clinical Symptoms Using The Gastrointestinal Symptom Rating Scale (GSRS) Score
Description	The GSRS has a seven-point graded Likert-type scale where 1 represents absence of troublesome symptoms and 7 represents very troublesome symptoms. A higher GSRS indicate worse symptoms and a difference between D30 and last SBCE scores greater or equal to 0.3 can be considered as a clinically significant improvement in the symptoms.
Time Frame	one month

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Kidney Transplant Recipients With GI Symptoms
Arm/Group Description	If there are negative findings on SBCE, that will be continued on MMF. No need to have second SBCE. Small bowel capsule endoscopy (SBCE): SBCE will be performed at Day 2 and Day 30. Small bowel capsule endoscopy (SBCE): SBCE will be performed at Day 2.
Measure Participants	18
baseline	2.99
day 30	2.19

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Kidney Transplant Recipients With GI Symptoms
	Comments	The results of the initial SBCE exams were evaluated by a visually challenged GI specialist who gave us a descriptive report. By the end of the study, we submitted the final reports to the same specialist and asked his impression on the significant changes observed in patients' exams for each GI segment (stomach and small bowel). There were no comparison groups. Each patient is their own control. Given that this is a pilot study there is no power calculation.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.05
	Comments	The p value is only for GSRS score comparison only.
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0
	Confidence Interval	(2-Sided) 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	The GSRS range is 1-7

Adverse Events

Arm/Group Title	Kidney Transplant Recipients With GI Symptoms
Arm/Group Description	If there are negative findings on SBCE, that will be continued on MMF. No need to have second SBCE. Small bowel capsule endoscopy (SBCE): SBCE will be performed at Day 2 and Day 30. Small bowel capsule endoscopy (SBCE): SBCE will be performed at Day 2.
All Cause Mortality
	Kidney Transplant Recipients With GI Symptoms
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Kidney Transplant Recipients With GI Symptoms
	Affected / at Risk (%)	# Events
Total	0/23 (0%)
Other (Not Including Serious) Adverse Events
	Kidney Transplant Recipients With GI Symptoms
	Affected / at Risk (%)	# Events
Total	0/23 (0%)

Limitations/Caveats

We did not enroll asymptomatic patients and in the extension of the trial the number of patients re-examined were few and the data obtained from them are not enough to provide definitive information.

More Information

Certain Agreements

Principal Investigators are NOT 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.