Metabolic and Infectious Complications Post Belatacept Conversion (Belaswitch)

Study of the Impact of Belatacept Conversion on Metabolic and Infectious Complications in Kidney Transplant Recipients at Grenoble-Alpes University Hospital

The BELASWITCH study is a prospective single-centre study including all kidney transplant patients for whom a conversion from Tacrolimus to Belatacept has been decided by the transplant clinicians of the Grenoble Alpes University Hospital.

Each patient will be included at the time of conversion (patients stable on Tacrolimus for at least 6 months) and will be their own control 1 year after conversion to Belatacept.

The study has two components:

• A "Metabolic" benefit arm: the investigators assume that conversion from Tacrolimus to Belatacept reduces the risk of diabetes by reducing the level of insulin resistance.
• An "Infectious" risk arm: measurement of the viral load of Torque Teno Virus to assess the state of immunosuppression of patients. In this sense, the investigators hypothesise that it could serve as a biomarker of immunodepression in this population.

Study Overview

• Status: Not yet recruiting
• Conditions: Cardiovascular Diseases; Kidney Transplant Infection; Immunosuppression; Kidney Transplant; Complications
• Intervention / Treatment: Diagnostic test: Oral glucose tolerance test

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

• Study Contact: Name: Johan Noble, M.D.; Phone Number: +33 4 76 76 74 73; Email: jnoble@chu-grenoble.fr
• Study Contact Backup: Name: Claire Bollart; Phone Number: +33 4 76 76 68 14; Email: CBollart@chu-grenoble.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The BELASWITCH study cohort is a prospective single-centre study including all adult kidney transplant recipients for whom a conversion from Tacrolimus to Belatacept has been decided by the transplant clinicians of the Grenoble Alpes University Hospital.

Each patient will be included at the time of conversion (patients stable on Tacrolimus for at least 6 months) and will be their own control 1 year after conversion to Belatacept.

Description

Inclusion Criteria:

• Adult patients who have had a kidney transplant more than 6 months ago.
• Whose immunosuppression includes stable Tacrolimus (change in dose or dosage form allowed) for at least 3 months.
• Therapeutic plan to change Tacrolimus-based immunosuppression to Belatacept
• Having signed the consent of collection CRB04 - Nephrology Collection (last authorization number: AC-2019-3627) and the BELASWITCH protocol consent.

Exclusion Criteria:

• Subjects under guardianship or deprived of liberty
• Patients who object to the use of their data and/or samples in the research
• Patients having received an immunosuppressive treatment different from the standard one (Tacrolimus, mycophenolate mofetil or Everolimus, corticosteroids)
• ABO and/or HLA incompatible kidney transplantation

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Belatacept cohort; Kidney transplanted patients for whom a conversion from Tacrolimus to belatacept has been decided will be included in this cohort.	Diagnostic test: Oral glucose tolerance test; The test is performed on an empty stomach for at least 10 hours. The first blood sugar level is taken on an empty stomach. Then ingestion of 75g of sugar. A second blood test takes place 1 hour after the sugar intake and the third blood sugar test takes place 2 hours after the sugar intake.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Oral glucose tolerance test results in kidney transplant patients on Tacrolimus (M-1 and D0) and after conversion to Belatacept at 1 year	1 year
Torque TenoVirus replication (in copies/ml) in kidney transplant patients on Tacrolimus (M-1 and D0) and after conversion to Belatacept at 3 months, 6 months and 1 year.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of weight and height (combined to report BMI in kg/m^2) on Tacrolimus (M-1 and D0) and after conversion to Belatacept at 3 months, 6 months and 1 year		1 year
Comparison of blood pressure in mmHg on Tacrolimus (M-1 and D0) and after conversion to Belatacept at 3 months, 6 months and 1 year		1 year
Comparison of abdominal perimeter of kidney transplant recipients in centimeters on Tacrolimus (M-1 and D0) and after conversion to Belatacept at 3 months, 6 months and 1 year		1 year
Comparison of HbA1c measurment in percentage on Tacrolimus (M-1 and D0) and after conversion to Belatacept at 3 months, 6 months and 1 year		1 year
Comparison of LDL measurment in g/l on Tacrolimus (M-1 and D0) and after conversion to Belatacept at 3 months, 6 months and 1 year		1 year
Comparison of HDL measurment in g/l on Tacrolimus (M-1 and D0) and after conversion to Belatacept at 3 months, 6 months and 1 year		1 year
Comparison of triglycerides measurment in g/l on Tacrolimus (M-1 and D0) and after conversion to Belatacept at 3 months, 6 months and 1 year		1 year
Number of major cardiovascular events (stroke, coronary syndrome, hospitalization for cardiac decompensation, death from cardiovascular causes)		1 year
Correlation of TorqueTenoVirus replication in copies/ml with the occurrence of opportunistic infections (Cytomegalovirus, Epstein-Barr virus, BKVirus).	Opportunistic infections are defined as positive DNAemia in copies/ml	1 year
Correlatation of TorqueTenoVirus replication (in copies/ml) with immunosuppressant assays: Tacrolimus (µg/l) at M-1 and D0 and Belatacept (µg/l) at M3, M6 and M12		1 year
Correlation of TorqueTenoVirus in copies/ml and the risk of biopsy-proven renal transplant rejection up to M12 after conversion to Belatacept.	Rejection are defined according to the more recent histological Banff classification	1 year
Compare the performance of TorqueTenoVirus quantitative polymerase chain reaction in copies/ml performed on plasma and whole blood samples		3 months
Trough Plasma Concentration of Belatacept		3 months
Area under the plasma concentration versus time curve (AUC) of Belatacept		3 months

Collaborators and Investigators

• Sponsor: University Hospital, Grenoble

Publications and helpful links

General Publications

• Collins AJ, Foley RN, Gilbertson DT, Chen SC. United States Renal Data System public health surveillance of chronic kidney disease and end-stage renal disease. Kidney Int Suppl (2011). 2015 Jun;5(1):2-7. doi: 10.1038/kisup.2015.2.
• Dharnidharka VR. Costimulation blockade with belatacept in renal transplantation. N Engl J Med. 2005 Nov 10;353(19):2085-6; author reply 2085-6. doi: 10.1056/NEJM200511103531919. No abstract available.
• Vincenti F, Rostaing L, Grinyo J, Rice K, Steinberg S, Gaite L, Moal MC, Mondragon-Ramirez GA, Kothari J, Polinsky MS, Meier-Kriesche HU, Munier S, Larsen CP. Belatacept and Long-Term Outcomes in Kidney Transplantation. N Engl J Med. 2016 Jan 28;374(4):333-43. doi: 10.1056/NEJMoa1506027. Erratum In: N Engl J Med. 2016 Feb 18;374(7):698.
• Durrbach A, Pestana JM, Florman S, Del Carmen Rial M, Rostaing L, Kuypers D, Matas A, Wekerle T, Polinsky M, Meier-Kriesche HU, Munier S, Grinyo JM. Long-Term Outcomes in Belatacept- Versus Cyclosporine-Treated Recipients of Extended Criteria Donor Kidneys: Final Results From BENEFIT-EXT, a Phase III Randomized Study. Am J Transplant. 2016 Nov;16(11):3192-3201. doi: 10.1111/ajt.13830. Epub 2016 Jun 9.
• Baron PW, Infante S, Peters R, Tilahun J, Weissman J, Delgado L, Kore AH, Beeson WL, de Vera ME. Post-Transplant Diabetes Mellitus After Kidney Transplant in Hispanics and Caucasians Treated with Tacrolimus-Based Immunosuppression. Ann Transplant. 2017 May 23;22:309-314. doi: 10.12659/aot.903079.
• Iida S, Ishida H, Tokumoto T, Omoto K, Shirakawa H, Shimizu T, Amano H, Setoguchi K, Nozaki T, Toki D, Tokita D, Tanabe K. New-onset diabetes after transplantation in tacrolimus-treated, living kidney transplantation: long-term impact and utility of the pre-transplant OGTT. Int Urol Nephrol. 2010 Dec;42(4):935-45. doi: 10.1007/s11255-010-9712-0. Epub 2010 Feb 19.
• Drachenberg CB, Klassen DK, Weir MR, Wiland A, Fink JC, Bartlett ST, Cangro CB, Blahut S, Papadimitriou JC. Islet cell damage associated with tacrolimus and cyclosporine: morphological features in pancreas allograft biopsies and clinical correlation. Transplantation. 1999 Aug 15;68(3):396-402. doi: 10.1097/00007890-199908150-00012.
• Terrec F, Jouve T, Naciri-Bennani H, Benhamou PY, Malvezzi P, Janbon B, Giovannini D, Rostaing L, Noble J. Late Conversion From Calcineurin Inhibitors to Belatacept in Kidney-Transplant Recipients Has a Significant Beneficial Impact on Glycemic Parameters. Transplant Direct. 2019 Dec 24;6(1):e517. doi: 10.1097/TXD.0000000000000964. eCollection 2020 Jan.
• Rangaswami J, Mathew RO, Parasuraman R, Tantisattamo E, Lubetzky M, Rao S, Yaqub MS, Birdwell KA, Bennett W, Dalal P, Kapoor R, Lerma EV, Lerman M, McCormick N, Bangalore S, McCullough PA, Dadhania DM. Cardiovascular disease in the kidney transplant recipient: epidemiology, diagnosis and management strategies. Nephrol Dial Transplant. 2019 May 1;34(5):760-773. doi: 10.1093/ndt/gfz053.
• Anavekar NS, McMurray JJ, Velazquez EJ, Solomon SD, Kober L, Rouleau JL, White HD, Nordlander R, Maggioni A, Dickstein K, Zelenkofske S, Leimberger JD, Califf RM, Pfeffer MA. Relation between renal dysfunction and cardiovascular outcomes after myocardial infarction. N Engl J Med. 2004 Sep 23;351(13):1285-95. doi: 10.1056/NEJMoa041365.
• Nankivell BJ, P'Ng CH, O'Connell PJ, Chapman JR. Calcineurin Inhibitor Nephrotoxicity Through the Lens of Longitudinal Histology: Comparison of Cyclosporine and Tacrolimus Eras. Transplantation. 2016 Aug;100(8):1723-31. doi: 10.1097/TP.0000000000001243.
• Bertrand D, Terrec F, Etienne I, Chavarot N, Sberro R, Gatault P, Garrouste C, Bouvier N, Grall-Jezequel A, Jaureguy M, Caillard S, Thervet E, Colosio C, Golbin L, Rerolle JP, Thierry A, Sayegh J, Janbon B, Malvezzi P, Jouve T, Rostaing L, Noble J. Opportunistic Infections and Efficacy Following Conversion to Belatacept-Based Therapy after Kidney Transplantation: A French Multicenter Cohort. J Clin Med. 2020 Oct 28;9(11):3479. doi: 10.3390/jcm9113479.
• Everly MJ, Roberts M, Townsend R, Bray RA, Gebel HM. Comparison of de novo IgM and IgG anti-HLA DSAs between belatacept- and calcineurin-treated patients: An analysis of the BENEFIT and BENEFIT-EXT trial cohorts. Am J Transplant. 2018 Sep;18(9):2305-2313. doi: 10.1111/ajt.14939. Epub 2018 Jun 16.
• Bertrand D, Chavarot N, Gatault P, Garrouste C, Bouvier N, Grall-Jezequel A, Jaureguy M, Caillard S, Lemoine M, Colosio C, Golbin L, Rerolle JP, Thierry A, Sayegh J, Etienne I, Lebourg L, Sberro R, Guerrot D. Opportunistic infections after conversion to belatacept in kidney transplantation. Nephrol Dial Transplant. 2020 Feb 1;35(2):336-345. doi: 10.1093/ndt/gfz255.
• Noble J, Jouve T, Janbon B, Rostaing L, Malvezzi P. Belatacept in kidney transplantation and its limitations. Expert Rev Clin Immunol. 2019 Apr;15(4):359-367. doi: 10.1080/1744666X.2019.1574570. Epub 2019 Feb 7.
• Noble J, Langello A, Bouchut W, Lupo J, Lombardo D, Rostaing L. Immune Response Post-SARS-CoV-2 mRNA Vaccination in Kidney Transplant Recipients Receiving Belatacept. Transplantation. 2021 Nov 1;105(11):e259-e260. doi: 10.1097/TP.0000000000003923. No abstract available.
• Strassl R, Doberer K, Rasoul-Rockenschaub S, Herkner H, Gorzer I, Klager JP, Schmidt R, Haslacher H, Schiemann M, Eskandary FA, Kikic Z, Reindl-Schwaighofer R, Puchhammer-Stockl E, Bohmig GA, Bond G. Torque Teno Virus for Risk Stratification of Acute Biopsy-Proven Alloreactivity in Kidney Transplant Recipients. J Infect Dis. 2019 May 24;219(12):1934-1939. doi: 10.1093/infdis/jiz039.
• Doberer K, Haupenthal F, Nackenhorst M, Bauernfeind F, Dermuth F, Eigenschink M, Schiemann M, Klager J, Gorzer I, Eskandary F, Reindl-Schwaighofer R, Kikic Z, Bohmig G, Strassl R, Regele H, Puchhammer-Stockl E, Bond G. Torque Teno Virus Load Is Associated With Subclinical Alloreactivity in Kidney Transplant Recipients: A Prospective Observational Trial. Transplantation. 2021 Sep 1;105(9):2112-2118. doi: 10.1097/TP.0000000000003619.
• Sharts-Hopko NC. Hormone replacement therapy and cardiovascular health in midlife women. Medsurg Nurs. 1995 Aug;4(4):314-6. No abstract available.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): June 1, 2022
• Primary Completion (ANTICIPATED): June 1, 2023
• Study Completion (ANTICIPATED): June 1, 2024

Study Registration Dates

• First Submitted: March 21, 2022
• First Submitted That Met QC Criteria: March 29, 2022
• First Posted (ACTUAL): April 7, 2022

Study Record Updates

• Last Update Posted (ACTUAL): April 7, 2022
• Last Update Submitted That Met QC Criteria: March 29, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: transplantation; Belatacept; TTV; Cardio-vascular complications
• Additional Relevant MeSH Terms: Cardiovascular Diseases
• Other Study ID Numbers: Belaswitch_Grenoble

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No