Clinical trial NCT01109914: Mucosal Response in Immunocompromised Host
Official title: Immune Response After Inactivated Oral Cholera Vaccine (Dukoral) in Renal Transplant Recipients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Kidney Transplantation
Immunity
Keywords: Renal transplantation
Immunosuppression
ETEC
Dukoral
Vaccination
Immunity, Humoral
Lead sponsor: Leiden University Medical Center
Sponsor class: OTHER
Collaborators: name: Crucell B.V., Leiden, the Netherlands
First posted: 2010-04-23
Enrollment: 51
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The aim of this study is to verify whether vaccination with Dukoral® (SBL Vaccines) induces an immune response in renal transplant recipients on prednisolone in combination with either a calcineurin inhibitor CNI) or mycophenolate mofetil (MMF).

Detailed description: BACKGROUND:

LT-ETEC is the most common cause of travelers' diarrhoea. Dukoral® (SBL Vaccines) reduces the severity and duration of LT-ETEC induced diarrhea. Dehydration due to diarrhea poses a risk to the health of renal transplant recipients. Therefore Dukoral may benefit this group of travelers.

AIM OF THIS STUDY:

Primary objective: To verify whether vaccination with Dukoral® (SBL Vaccines) induces an immune response in renal transplant recipients on prednisolone in combination with either a calcineurin inhibitor (cyclosporine or tacrolimus) or mycophenolate mofetil.

Secondary objective: To evaluate to what extent, the immune response differs, depending on the use of different classes of immunosuppressive drugs (CNI or MMF).

STUDY DESIGN:

Single center interventional study.

Population: The population base of the study consists of adult renal transplant recipients who received their transplant at our medical center. The control population consists of the healthy partners and siblings of the renal transplant recipients. We intend to include 10 healthy volunteers and 60 renal transplant recipients (20 on prednisolone and a CNI and 20 on prednisolone and MMF).

Intervention: Dukoral® (SBL Vaccines) will be administered orally at baseline (day 0) and at day 14.

Laboratory analysis: Serum CTB antibody (ELISA), Vibriocidal assay. The analysis is performed at Crucell.

Statistical analysis: No formal sample-size calculation was performed. The crude outcome estimates will be adjusted for variables that may influence the outcome (age, time after transplantation, past treatment for transplant rejection, current renal function, cumulative prednisolone dose, serum concentration (i.e. area under the curve) of CNI and MMF.

Note: the study intended to also recruit a study arm consisting of patients on a mTORi. Recruitment for this study arm was unsuccesful due to the scarcity of elligible patients.

Eligibility criteria: HEALTHY VOLUNTEERS

Inclusion criteria:

* Above 18 years of age
* Informed consent

Exclusion Criteria:

* History of an auto-immune disease (SLE, ANCA associated vasculitis, Goodpasture, Henoch Schonlein, cryoglobulinemia, secondary vasculitis, polyarteritis nodosa and immunodeficiency disorders like IgA deficiency)
* Chronic infection
* Past vaccination with Dukoral or another cholera or ETEC vaccine
* History of infection with Vibrio cholerae
* Episode of diarrhoea in the 6 months prior to inclusion
* Allergy to vaccine-specific components
* History of a severe allergic reaction to any vaccine
* Treatment with blood products in the 3 months prior to inclusion
* Current pregnancy or breastfeeding
* Premenopausal women not willing to use contraceptives during the first 60 days after vaccination
* Use of any immunosuppressive drug

RENAL TRANSPLANT RECIPIENTS

Inclusion Criteria:

* Above 18 years of age
* Creatinin clearance ≥ 40 ml/min measured in the 6 months prior to inclusion
* Stable renal function for 1 year prior to inclusion
* Stable immunosuppressive regimen of a CNI, MMF or mTORi combined with prednisolone for at least 3 months prior to inclusion
* Informed Consent

Exclusion Criteria:

* History of an auto-immune disease (SLE, ANCA associated vasculitis, Goodpasture, Henoch Schonlein, cryoglobulinemia, secondary vasculitis, polyarteritis nodosa and immunodeficiency disorders like IgA deficiency)
* Chronic infection
* Treatment for rejection of the transplant in the past 1 year prior to inclusion
* Past vaccination with Dukoral or another cholera or ETEC vaccine
* History of infection with Vibrio cholerae
* Episode of diarrhoea in the 6 months prior to inclusion
* Allergy to vaccine-specific components
* History of a severe allergic reaction to any vaccine
* Treatment with blood products in the 3 months prior to inclusion
* Current pregnancy or breastfeeding
* Premenopausal women not willing to use contraceptives during the first 60 days after vaccination
* Use of an immunosuppressive drug other than CNI, MMF, mTORi or prednisolone at the the time of inclusion

Primary outcomes:
measure: Percentage seroconversion among all renal transplant recipients.
timeFrame: day 20-22
Secondary outcomes:
measure: Group differences in geometric mean antibody titers after vaccination
timeFrame: day 20-22
Other outcomes:
Locations:
city: Leiden
country: Netherlands
facility: Leiden Univeristy Medical Centre
state: Zuid-Holland
Study officials:
affiliation: Leiden University Medical Center
name: Leo G Visser, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Leiden University Medical Center
name: Darius Soonawala, MD
role: STUDY_DIRECTOR
affiliation: Leiden University Medical Center
name: O W Bredewold, MD
role: STUDY_CHAIR
affiliation: Leiden University Medical Center
name: J W de Fijter, Prof PhD
role: STUDY_CHAIR
affiliation: Leiden University Medical Center
name: Marjolein AC Uijlings
role: STUDY_CHAIR
affiliation: Leiden University Medical Center
name: Emile FF Jonker, MD
role: STUDY_CHAIR
References:
citation: Jonker EFF, Uijlings MAC, Visser LG, Soonawala D. Comparison of the immunogenicity of Dukoral(R) oral cholera vaccine between renal transplant recipients on either a calcineurin inhibitor or mycophenolate - A controlled trial. Vaccine. 2019 May 21;37(23):3133-3139. doi: 10.1016/j.vaccine.2019.04.010. Epub 2019 Apr 24.