Gastrointestinal Lesions, Signs and Symptoms, Digestive
Conditions
Keywords
Renal transplant recipients, Gastrointestinal findings in small bowel capsule endoscopy, Mycophenolic acid, Mycophenolate Mofetil, Mycophenolate Sodium
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).
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.
Interventions
PROCEDURESmall bowel capsule endoscopy (SBCE)
SBCE will be performed at Day 2 and Day 30.
DRUGmyfortic
switching from mycophenolate mofetil to mycophenolic acid on equimolar basis
Sponsors
Novartis
University of California, Los Angeles
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Recruitment details
Kidney Transplant Clinic
Participants by arm
| Arm | Count |
|---|---|
| Kidney Transplant Recipients With GI Symptoms 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. | 18 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Kidney Transplant Recipients With GI Symptoms |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 17 Participants |
| Age, Continuous | 45 years STANDARD_DEVIATION 11.69 |
| Region of Enrollment United States | 18 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 23 |
| serious Total, serious adverse events | 0 / 23 |
Outcome results
Primary
GI Mucosal Lesions Change and Clinical Symptoms Using The Gastrointestinal Symptom Rating Scale (GSRS) Score
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
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Kidney Transplant Recipients With GI Symptoms | GI Mucosal Lesions Change and Clinical Symptoms Using The Gastrointestinal Symptom Rating Scale (GSRS) Score | baseline | 2.99 GSRS score |
| Kidney Transplant Recipients With GI Symptoms | GI Mucosal Lesions Change and Clinical Symptoms Using The Gastrointestinal Symptom Rating Scale (GSRS) Score | day 30 | 2.19 GSRS score |
Comparison: 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.p-value: 0.05t-test, 2 sided