Mucosal Response in Immunocompromised Host

Kidney Transplantation Clinical Trial

— MICH  

Official title:

Immune Response After Inactivated Oral Cholera Vaccine (Dukoral) in Renal Transplant Recipients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01109914
• Other study ID #: MICH P10.011
• Status: Completed
• Phase: Phase 4
• First received: April 22, 2010
• Last updated: March 25, 2015
• Start date: April 2010
• Est. completion date: March 2015

Study information

• Verified date: March 2015
• Source: Leiden University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 51
• Est. completion date: March 2015
• Est. primary completion date: March 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Immunity
• Kidney Transplantation

Intervention

Biological:
• Dukoral
Two oral doses of Dukoral® (SBL Vaccines) will be administered (day 0 and day 14). Each dosage contains 3 ml of suspension in a vial and 5.6 g of effervescent granules in a sachet. Each dosage (3 ml) contains: A total of 100000 million bacteria of the following strains: Vibrio cholerae O1 Inaba, classical biotype (heat inactivated) 25x1000 million bacteria* Vibrio cholerae O1 Inaba, El Tor biotype (formalin inactivated) 25x1000 million bacteria* Vibrio cholerae O1 Ogawa, classical biotype (heat inactivated) 25x1000 million bacteria* Vibrio cholerae O1 Ogawa, classical biotype (formalin inactivated) 25x1000 million bacteria* -Recombinant cholera toxin B subunit (rCTB) 1 mg (produced in V. cholerae O1 Inaba, classical biotype strain 213)

Locations

Country	Name	City	State
Netherlands	Leiden Univeristy Medical Centre	Leiden	Zuid-Holland

Sponsors (2)

Lead Sponsor	Collaborator
Leiden University Medical Center	Crucell B.V., Leiden, the Netherlands

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage seroconversion among all renal transplant recipients.	=3-fold rise in serum anti-CTB antibodies or =4-fold rise in serum vibriocidal antibodies.	day 20-22	No
Secondary	Group differences in geometric mean antibody titers after vaccination	post-vaccination anti-rCTB titers, measured by Enzyme Immuno Assay (EIA); post-vaccination serum vibriocidal antibodies, measured in vibriocidal assay.	day 20-22	No