Mucosal Response in Immunocompromised Host (MICH)

March 25, 2015 updated by: Darius Soonawala, Leiden University Medical Center

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

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

51

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
    • Zuid-Holland
      • Leiden, Zuid-Holland, Netherlands, 2333 ZA
        • Leiden univeristy medical centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Renal transplant recipients (MMF)

Renal transplant recipients using prednisolone and mycophenolate mofetil (MMF) but no other immunosuppressive drug.

Intervention: vaccination with Dukoral
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)
Experimental: Renal transplant recipients (CNI)

Renal transplant recipients using prednisolone and a calcineurin inhibitor (cyclosporine or tacrolimus) but no other immunosuppressive drug.

Intervention: vaccination with Dukoral
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)
Experimental: Healthy volunteers

Healthy volunteers (partners, brothers or sisters of the renal transplant recipients).

Intervention: vaccination with Dukoral
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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage seroconversion among all renal transplant recipients.
Time Frame: day 20-22
≥3-fold rise in serum anti-CTB antibodies or ≥4-fold rise in serum vibriocidal antibodies.
day 20-22

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Group differences in geometric mean antibody titers after vaccination
Time Frame: day 20-22
post-vaccination anti-rCTB titers, measured by Enzyme Immuno Assay (EIA); post-vaccination serum vibriocidal antibodies, measured in vibriocidal assay.
day 20-22

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Leiden University Medical Center

Collaborators

Crucell B.V., Leiden, the Netherlands

Investigators

  • Principal Investigator: Leo G Visser, MD PhD, Leiden University Medical Center
  • Study Director: Darius Soonawala, MD, Leiden University Medical Center
  • Study Chair: O W Bredewold, MD, Leiden University Medical Center
  • Study Chair: J W de Fijter, Prof PhD, Leiden University Medical Center
  • Study Chair: Marjolein AC Uijlings, Leiden University Medical Center
  • Study Chair: Emile FF Jonker, MD, Leiden University Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2010

Primary Completion (Actual)

March 1, 2015

Study Completion (Actual)

March 1, 2015

Study Registration Dates

First Submitted

April 22, 2010

First Submitted That Met QC Criteria

April 22, 2010

First Posted (Estimate)

April 23, 2010

Study Record Updates

Last Update Posted (Estimate)

March 26, 2015

Last Update Submitted That Met QC Criteria

March 25, 2015

Last Verified

March 1, 2015

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • MICH P10.011

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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