Systemic SclerosisMMFSSCNCT03678987
Mycophenolate Mofetil Pharmacokinetics in Systemic Sclerosis
An observational study of Systemic Sclerosis and Gastrointestinal Complication, run by Region Skane at 1 site in Sweden.
Trial summary
Drug of investigation: Mycophenolate mofetil (MMF), given orally as a tablet twice daily. Dosage of drug: This study recruits patients who have been prescribed a steady dose of MMF in the range between 1000 and 3000 mg daily by their physician. Design: This is an open-label PK study. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Systemic Sclerosis, Gastrointestinal Complication
- What is being tested?
- P-MPA concentration and mycophenolic acid
- How many people
- 35 participants
- Where
- 1 siteSweden
- Study dates
- 13 Sep 2018to 1 Feb 2020
- Phase
- Observational
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with systemic sclerosis using a stable dose of mycophenolate mofetil.
Who may be able to join
- a confirmed diagnosis of SSC according to the 2013 ACR/EULAR classification criteria
- above 18 years of age
- fluent in Swedish and able to understand the study protocol and "Patient information"
- being prescribed and using a fixed dos (1000-3000 mg daily) of MMF tablet, Cellcept or substitutable medical product, twice daily since at least 3 months
- the study participant's written and informed consent
- women in child-bearing age should use contraception
Who cannot join
- Recipient of a solid organ transplant
- Pregnancy or lactation
- The presence of renal failure (defined as eGFR < 30 ml/min)
- A history of complicated venipunctures defined as
- a history of any venipuncture within the last year that required three or more attempts in order to succeed or
- a decision has been made that the patient should receive a subcutaneous venous port because of complicated venipunctures.
Show all 12Show fewer
- If the patient has a functioning subcutaneous venous port, the above criteria does not apply if venous sampling has been uncomplicated from this port.
- A history of hypersensitivity reactions to MMF
- Patients diagnosed with any kind of acute infection during the one (1) week preceding the study day
- A history of gastrointestinal surgery that includes resection of any port of the ventricle, small intestine, large intestine or liver (except for surgery for appendicitis, gall bladder resection or hemorrhoids, which do not constitute reasons for exclusion)
- Pulmonary arterial hypertension
- Anemia, defined as Hb < 100 g/L during the last 4 weeks The patient will be informed about the study and sign informed consent before study commences.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Mycophenolate Mofetil in Systemic Sclerosis: A Phase 1 Pharmacokinetic Study of Orally Ingested Mycophenolate Mofetil Tablets in Patients Suffering From Systemic Sclerosis
Drug of investigation: Mycophenolate mofetil (MMF), given orally as a tablet twice daily.
Dosage of drug: This study recruits patients who have been prescribed a steady dose of MMF in the range between 1000 and 3000 mg daily by their physician.
Read more
Design: This is an open-label PK study.
Disease studied: Systemic sclerosis (SSC, scleroderma).
Variables assessed: Estimated AUC0-12 for MMF. Gastrointestinal manifestations of SSc. Concomitant medication.
Study population:
Inclusion criteria: Diagnosis of SSC fulfilling the 2013 classification criteria for this disease. Participant should have been prescribed a stable dose of MMF tablets, taken twice daily, for at least 3 months prior to the study.
Exclusion criteria: Failure to comply with study protocol. Limited access to repeated venous puncture. Recipient of organ transplant. Pulmonary arterial hypertension.
Number of participants: The study aims at the inclusion of 35 subjects.
Primary objective: To investigate the PK of orally ingested MMF in SSC.
Secondary objectives:
- To investigate how SSC manifested in the gastrointestinal (GI) tract may alter the PK of MMF.
- To investigate how the PK of MMF in SSc is altered by medications often used in SSC, i.e. proton pump inhibitors (PPI), NSAID and calcium channel blockers.
Read the detailed description
DESIGN AND ASSESSMENT SCHEDULE Study participants will take their medication, including the study drug, as prescribed by their ordinary physician. Study participant will note what they had for breakfast.
The study-timespan for the individual study participant is estimated to maximum 8 hours.
Blood samples will be drawn from a subcutaneous venous port if available. If not available, subjects will be receive a peripheral venous catheter that is to be used for repeated blood sampling. If usage of such a catheter fails during the study day, blood samples will be drawn from repeated venipunctures.
VARIABLES STUDIED
The following variables will be studied:
Plasma-MMF-concentration: Will be measured by approved laboratory, Skåne UniversityHospital, using high performance liquid chromatography. AUC 0_12 will be calculated as suggested by de Winter, Neumann, van Hest et. al., Ther Drug Mon 2009;31(3):382-390.
Kidney and liver function: Serum samples will be analysed regarding kidney function and eGFR will be calculated from creatinin and cystatin C. Liver function will be assessed by AST, ALT, GT and ALP. Hematological characteristics will be noted.
GI manifestations of SSc: Fecal calprotectin, will be assayed by ELISA (Calpro, Lysaker, Norway) at University Hospital Lund. Malnutrition will evaluated in reference to the validated Malnutrition Universal Screening Tool (MUST). S-transthyretin, vitamin B12, folic acid, iron and zink and S-albumin will be assessed as markers of malnutrition. The intestinal flora will be assessed by microbiological analysis of fecal sampling (Genetic Analysis AS, Oslo, Norway).
Pregnancy: Will be evaluated by urine test.
Questionnaire: Regarding concomitant medication and the UCLA SCTC GIT 2.0 (Swedish version) will be given to each study participant.
- Conditions
- Systemic Sclerosis, Gastrointestinal Complication
- Being tested
- P-MPA concentration, mycophenolic acid
- Keywords
- pharmacokinetics, mycophenolate mofetil
- Medical subject headings
- Scleroderma, Systemic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
P-MPA concentrationDiagnostic test
We will calculate AUC_0-12 of MPA based on 4 measurements of P-MPA
mycophenolic acidDrug
Also called cellcept, mycophenolate mofetil
Patient will ingest mycophenolic acid as prescribed by their physician under the surveillance of an investigator.
| Study group | Role | What they receive |
|---|---|---|
| SSc on MMF | Patients with systemic sclerosis using mycophenolate mofetil (mycophenolic acid, MMF) since >3 months.
During a 6 hour time period, P-MPA concentration will be measured 4 times. Receives: Diagnostic Test: P-MPA concentration; Drug: mycophenolic acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Individual plasma concentrations of mycophenolic acid
By 4 measurements of P-MPA during a 6 hour time period we will estimate the individual drug exposition expressed as Area Under the Curve (AUC) 0-12 for this medicine and calculated as suggested by Abd Rahman 2014 (reference 3).
Measured: 1 day
Secondary outcomes (5)
Correlation between F-calprotectin and the AUC of P-MPA
To investigate how gastrointestinal inflammation as measured by F-calprotectin correlate with the AUC of P-MPA
Measured: 1 day
Correlation between the USCLA SCTC GIT-2.0 questionnaire and the AUC of P-MPA
To investigate how the gastrointestinal manifestations of SSc, assessed by a SSc-specific questionnaire, correlate with the AUC of P-MPA
Measured: 1 day
Correlation between the Malnutrition Universal Screening Tool (MUST) and the AUC of P-MPA
To investigate if malnutrition, assessed by the MUST, correlate with the AUC of P-MPA
Measured: 1 day
Correlation between the precense of dysbiosis, as defined by the GA-MAP Dysbiosis Test and the AUC of P-MPA
To investigate if intestinal dysbiosis, assessed by the a validated test available through Genetic Analysis, Oslo Norway, is associated with the AUC of P-MPA
Measured: 1 day
Association between the AUC of P-MPA and the concomitant medication with a) NSAID, b) proton-pump inhibitors and c) Ca-channel blockers
To compare the AUC of P-MPA in patients with and without the above mentionened concomitant medication
Measured: 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Sep 2018
- Study start13 Sep 2018
- Primary completion1 Jan 2020
- Study completion1 Feb 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Systemic SclerosisStudies of the same condition, open and under way.
- More trials run by Region SkaneThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- Region Skane
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kristofer Andreasson, Region Skane
- Investigators
- Kristofer Andréasson, MD PhD, Principal investigator, Region Skane
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03678987
- Sponsor's protocol ID
- 2018-002105-54
- Other IDs
- 2018
- Acronym
- MMFSSC
- Status last verified
- Mar 2020
- First submitted
- 13 Sep 2018
- Last updated
- 13 Mar 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided: This issue will be discussed with the Ethical board.
Publications
Volkmann ER, Tashkin DP, Li N, Roth MD, Khanna D, Hoffmann-Vold AM, Kim G, Goldin J, Clements PJ, Furst DE, Elashoff RM. Mycophenolate Mofetil Versus Placebo for Systemic Sclerosis-Related Interstitial Lung Disease: An Analysis of Scleroderma Lung Studies I and II. Arthritis Rheumatol. 2017 Jul;69(7):1451-1460. doi: 10.1002/art.40114. Epub 2017 May 23.
PubMed 28376288McCune WJ, Al Abbas M. Mycophenolate mofetil, for rheumatic diseases: should we monitor the area under the curve? Curr Opin Rheumatol. 2018 May;30(3):229-230. doi: 10.1097/BOR.0000000000000501. No abstract available.
PubMed 29538009Abd Rahman AN, Tett SE, Staatz CE. How accurate and precise are limited sampling strategies in estimating exposure to mycophenolic acid in people with autoimmune disease? Clin Pharmacokinet. 2014 Mar;53(3):227-245. doi: 10.1007/s40262-013-0124-z.
PubMed 24327238de Winter BC, Neumann I, van Hest RM, van Gelder T, Mathot RA. Limited sampling strategies for therapeutic drug monitoring of mycophenolate mofetil therapy in patients with autoimmune disease. Ther Drug Monit. 2009 Jun;31(3):382-90. doi: 10.1097/FTD.0b013e3181a23f1a.
PubMed 19363460
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mycophenolate Mofetil in Systemic Sclerosis: A Phase 1 Pharmacokinetic Study of Orally Ingested Mycophenolate Mofetil Tablets in Patients Suffering From Systemic Sclerosis
- ClinicalTrials.gov ID
- NCT03678987
- Acronym / sponsor ID
- MMFSSC / 2018-002105-54
- Conditions
- Systemic Sclerosis, Gastrointestinal Complication
- Keywords
- pharmacokinetics, mycophenolate mofetil
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- Region SkaneUniversity, hospital or other
- Study start
- 13 Sep 2018 (actual)
- Primary completion
- 1 Jan 2020 (actual)
- Study completion
- 1 Feb 2020 (actual)
- First posted
- 20 Sep 2018 (actual)
- 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.
Drug of investigation: Mycophenolate mofetil (MMF), given orally as a tablet twice daily.
Dosage of drug: This study recruits patients who have been prescribed a steady dose of MMF in the range between 1000 and 3000 mg daily by their physician.
Design: This is an open-label PK study.
Disease studied: Systemic sclerosis (SSC, scleroderma).
Variables assessed: Estimated AUC0-12 for MMF. Gastrointestinal manifestations of SSc. Concomitant medication.
Study population:
Inclusion criteria: Diagnosis of SSC fulfilling the 2013 classification criteria for this disease. Participant should have been prescribed a stable dose of MMF tablets, taken twice daily, for at least 3 months prior to the study.
Exclusion criteria: Failure to comply with study protocol. Limited access to repeated venous puncture. Recipient of organ transplant. Pulmonary arterial hypertension.
Number of participants: The study aims at the inclusion of 35 subjects.
Primary objective: To investigate the PK of orally ingested MMF in SSC.
Secondary objectives:
- To investigate how SSC manifested in the gastrointestinal (GI) tract may alter the PK of MMF.
- To investigate how the PK of MMF in SSc is altered by medications often used in SSC, i.e. proton pump inhibitors (PPI), NSAID and calcium channel blockers.
Detailed description
DESIGN AND ASSESSMENT SCHEDULE Study participants will take their medication, including the study drug, as prescribed by their ordinary physician. Study participant will note what they had for breakfast.
The study-timespan for the individual study participant is estimated to maximum 8 hours.
Blood samples will be drawn from a subcutaneous venous port if available. If not available, subjects will be receive a peripheral venous catheter that is to be used for repeated blood sampling. If usage of such a catheter fails during the study day, blood samples will be drawn from repeated venipunctures.
VARIABLES STUDIED
The following variables will be studied:
Plasma-MMF-concentration: Will be measured by approved laboratory, Skåne UniversityHospital, using high performance liquid chromatography. AUC 0_12 will be calculated as suggested by de Winter, Neumann, van Hest et. al., Ther Drug Mon 2009;31(3):382-390.
Kidney and liver function: Serum samples will be analysed regarding kidney function and eGFR will be calculated from creatinin and cystatin C. Liver function will be assessed by AST, ALT, GT and ALP. Hematological characteristics will be noted.
GI manifestations of SSc: Fecal calprotectin, will be assayed by ELISA (Calpro, Lysaker, Norway) at University Hospital Lund. Malnutrition will evaluated in reference to the validated Malnutrition Universal Screening Tool (MUST). S-transthyretin, vitamin B12, folic acid, iron and zink and S-albumin will be assessed as markers of malnutrition. The intestinal flora will be assessed by microbiological analysis of fecal sampling (Genetic Analysis AS, Oslo, Norway).
Pregnancy: Will be evaluated by urine test.
Questionnaire: Regarding concomitant medication and the UCLA SCTC GIT 2.0 (Swedish version) will be given to each study participant.
Study design
- Observational model
- Other
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| SSc on MMF | – | Diagnostic Test: P-MPA concentration, Drug: mycophenolic acidPatients with systemic sclerosis using mycophenolate mofetil (mycophenolic acid, MMF) since >3 months. During a 6 hour time period, P-MPA concentration will be measured 4 times. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with systemic sclerosis using a stable dose of mycophenolate mofetil.
Key inclusion criteria (6 listed)
- a confirmed diagnosis of SSC according to the 2013 ACR/EULAR classification criteria
- above 18 years of age
- fluent in Swedish and able to understand the study protocol and "Patient information"
- being prescribed and using a fixed dos (1000-3000 mg daily) of MMF tablet, Cellcept or substitutable medical product, twice daily since at least 3 months
- the study participant's written and informed consent
Key exclusion criteria (12 listed)
- Recipient of a solid organ transplant
- Pregnancy or lactation
- The presence of renal failure (defined as eGFR < 30 ml/min)
- A history of complicated venipunctures defined as
- a history of any venipuncture within the last year that required three or more attempts in order to succeed or
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 |
|---|---|---|
| P-MPA concentrationWe will calculate AUC_0-12 of MPA based on 4 measurements of P-MPA | Diagnostic test | SSc on MMF |
| mycophenolic acidAlso: cellcept, mycophenolate mofetilPatient will ingest mycophenolic acid as prescribed by their physician under the surveillance of an investigator. | Drug | SSc on MMF |
Primary outcome
Individual plasma concentrations of mycophenolic acid
Time frame: 1 day
By 4 measurements of P-MPA during a 6 hour time period we will estimate the individual drug exposition expressed as Area Under the Curve (AUC) 0-12 for this medicine and calculated as suggested by Abd Rahman 2014 (reference 3).
5 secondary outcomes
Correlation between F-calprotectin and the AUC of P-MPA
Time frame: 1 day
Correlation between the USCLA SCTC GIT-2.0 questionnaire and the AUC of P-MPA
Time frame: 1 day
Correlation between the Malnutrition Universal Screening Tool (MUST) and the AUC of P-MPA
Time frame: 1 day
Correlation between the precense of dysbiosis, as defined by the GA-MAP Dysbiosis Test and the AUC of P-MPA
Time frame: 1 day
Association between the AUC of P-MPA and the concomitant medication with a) NSAID, b) proton-pump inhibitors and c) Ca-channel blockers
Time frame: 1 day
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 13 Mar 2020.
- Background: PubMed 28376288Volkmann ER, Tashkin DP, Li N, Roth MD, Khanna D, Hoffmann-Vold AM, Kim G, Goldin J, Clements PJ, Furst DE, Elashoff RM. Mycophenolate Mofetil Versus Placebo for Systemic Sclerosis-Related Interstitial Lung Disease: An Analysis of Scleroderma Lung Studies I and II. Arthritis Rheumatol. 2017 Jul;69(7):1451-1460. doi: 10.1002/art.40114. Epub 2017 May 23.
- Background: PubMed 29538009McCune WJ, Al Abbas M. Mycophenolate mofetil, for rheumatic diseases: should we monitor the area under the curve? Curr Opin Rheumatol. 2018 May;30(3):229-230. doi: 10.1097/BOR.0000000000000501. No abstract available.
- Background: PubMed 24327238Abd Rahman AN, Tett SE, Staatz CE. How accurate and precise are limited sampling strategies in estimating exposure to mycophenolic acid in people with autoimmune disease? Clin Pharmacokinet. 2014 Mar;53(3):227-245. doi: 10.1007/s40262-013-0124-z.
- Background: PubMed 19363460de Winter BC, Neumann I, van Hest RM, van Gelder T, Mathot RA. Limited sampling strategies for therapeutic drug monitoring of mycophenolate mofetil therapy in patients with autoimmune disease. Ther Drug Monit. 2009 Jun;31(3):382-90. doi: 10.1097/FTD.0b013e3181a23f1a.
- Individual participant dataSharing planned: Undecided. This issue will be discussed with the Ethical board.
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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.
Kristofer Andréasson, MD PhD principal investigator
Region Skane
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Systemic Sclerosis and Gastrointestinal Complication, run by Region Skane at 1 site in Sweden.
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 6 inclusion and 12 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 13 Mar 2020. 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 Sweden. 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.
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?
Individual plasma concentrations of mycophenolic acid (time frame: 1 day). 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 NCT03678987, which also lists 4 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 13 Mar 2020.