MAIDEN: Microsampling Assays for Immunosuppressive Drugs in Children

• Sponsor: Children's Hospital of Philadelphia (Other)
• Overall Status: Withdrawn
• CT.gov ID: NCT04989686
• Collaborator: (none)
• Enrollment: 0
• Location: 1

Study Details

Study Description

Brief Summary

Immunosuppressive therapy is used to treat and manage solid organ and bone marrow/stem cell transplants in children. However, it can be harmful if too little or too much is given. Monitoring immunosuppressive drug (cyclosporine A, tacrolimus, and sirolimus) concentrations in the blood is important to ensure that the drug is given safely and effectively, but current approaches for collecting blood from a vein are painful and often difficult in children. Investigators seek to compare a new approach for monitoring immunosuppressive drug concentrations using a novel small volume blood sampling technique to the traditional way of collecting blood from a vein.

The primary objective of this project is to identify the relationship between immunosuppressive drug (cyclosporine A, tacrolimus, and sirolimus) concentrations in the venous blood (gold-standard) and capillary whole blood obtained using microsampling.

The secondary objective of this study is to investigate the stability of blood samples containing immunosuppressive drugs (cyclosporine A, tacrolimus, and sirolimus) under the conditions of shipping and storage.

Condition or Disease	Intervention/Treatment	Phase
Immunosuppression	Other: Microsampling

Detailed Description

Immunosuppressive therapy is used to treat and manage solid organ and bone marrow/stem cell transplants; however, suboptimal dosing can lead to organ rejection and graft failure. Immunosuppressant drugs require therapeutic drug monitoring (TDM) to ensure dosing is adequate and therapeutic concentrations are achieved and maintained. The optimal blood concentrations of these drugs are critical to minimize toxicity and simultaneously prevent allograft rejection in an individual transplant patient. Often life-long TDM is required necessitating hospital or laboratory visits for routine venous blood sampling by phlebotomy. Immunosuppressive drugs, cyclosporine A (CYA), tacrolimus (TAC), and sirolimus (SIR) require routine TDM. This entails immunocompromised people leaving their homes for laboratory visits, potentially increasing their risk of acquiring infections.

TDM for CYA, TAC, and SIR are required due to their narrow therapeutic targets: CYA 150-400 ng/mL, TAC 5-12 ng/mL, and SIR 4-12 ng/mL. CYA, TAC, and SIR are primarily distributed in erythrocytes and should be quantified in whole blood. Immunoassays and the liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays are the two commonly used methods of TDM for CYA, TAC, and SIR. While immunoassays provide an accurate measurement of concentrations, they often have some limitations on specificity. LC-MS/MS assays are very specific and efficient since they can quantify multiple analytes with a single method. At the Children's Hospital of Philadelphia (CHOP), the clinical TDM immunoassays for CYA, TAC, and SIR require 0.5-1.0 mL of blood. TDM immunoassays require blood collection by a trained practitioner.

Volumetric absorptive microsampling (VAMS) with an FDA-approved Tasso-M20 device allows for the accurate and precise collection of a fixed volume of blood from a capillary needle without the need for phlebotomy. The Tasso-M20 (FDA Class 1 exempt device) consists of a sample head with a lancet that is activated with the push of a button to accurately and painlessly collect blood samples from the deltoid (or similar) muscle (capillary sampling) of the subjects on all four tips (20 µL each). An LC-MS/MS assay with 20 µL blood, as obtained by the Tasso device, was shown to provide the required test range for TDM of trough values. This microsampling technique could be utilized clinically to promote the provision of TDM in children but has not been studied for immunosuppressive drugs (CYA, TAC, and SIR) in children.

Study Design

• Study Type: Observational
• Actual Enrollment: 0 participants
• Observational Model: Other
• Time Perspective: Prospective
• Official Title: Microsampling Assays for Immunosuppressive Drugs in Children
• Anticipated Study Start Date: Mar 1, 2022
• Anticipated Primary Completion Date: Mar 1, 2022
• Anticipated Study Completion Date: Mar 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Cyclosporine A Males and females <18 years of age Greater than 5 kg Receiving cyclosporine A as the standard of care Has scheduled/anticipated blood draw to quantify the concentration of cyclosporine A for clinical indications Parental/guardian permission (informed consent), and subject's assent if applicable.	Other: Microsampling; Volumetric absorptive microsampling (VAMS) with Tasso-M20 devices allows for the accurate and precise collection of a fixed small volume of blood from a capillary needle without the need for phlebotomy.
Tacrolimus Males and females <18 years of age Greater than 5 kg Receiving tacrolimus as the standard of care Has scheduled/anticipated blood draw to quantify the concentration of tacrolimus for clinical indications Parental/guardian permission (informed consent), and subject's assent if applicable.	Other: Microsampling; Volumetric absorptive microsampling (VAMS) with Tasso-M20 devices allows for the accurate and precise collection of a fixed small volume of blood from a capillary needle without the need for phlebotomy.
Sirolimus Males and females <18 years of age Greater than 5 kg Receiving sirolimus as the standard of care Has scheduled/anticipated blood draw to quantify the concentration of sirolimus for clinical indications Parental/guardian permission (informed consent), and subject's assent if applicable.	Other: Microsampling; Volumetric absorptive microsampling (VAMS) with Tasso-M20 devices allows for the accurate and precise collection of a fixed small volume of blood from a capillary needle without the need for phlebotomy.

Outcome Measures

Primary Outcome Measures

1. Clinical validation of microsampling assay of Cyclosporin A [up to 20 months]

   Capillary whole blood specimens will be obtained via the Tasso M-20 sampling device to determine validity of the assay compared to venous blood samples (gold standard and used clinically) in measuring Cyclosporin A concentration levels.

2. Clinical validation of microsampling assay of Sirolimus [up to 20 months]

   Capillary whole blood specimens will be obtained via the Tasso M-20 sampling device to determine validity of the assay compared to venous blood samples (gold standard and used clinically) in measuring Sirolimus concentration levels.

3. Clinical validation of microsampling assay of Tacrolimus [up to 20 months]

   Capillary whole blood specimens will be obtained via the Tasso M-20 sampling device to determine validity of the assay compared to venous blood samples (gold standard and used clinically) in measuring Tacrolimus concentration levels.

Secondary Outcome Measures

1. Stability of blood samples containing immunosuppressive drug Cyclosporine A under conditions of shipping [up to 20 months]

   Blood specimens obtained by the Tasso M20 device will be used to investigate the stability of blood samples obtained by the Tasso M-20 device which contains immunosuppressive drugs cyclosporine A under the conditions of shipping

2. Stability of blood samples obtained which contains immunosuppressive drug Sirolimus under conditions of shipping [up to 20 months]

   Blood specimens obtained by the Tasso M20 device will be used to investigate the stability of blood samples obtained from the Tasso M-20 device containing immunosuppressive drugs sirolimus under the conditions of shipping

3. Stability of blood samples which contains immunosuppressive drug Tacrolimus under conditions of shipping [up to 20 months]

   Blood specimens obtained by the Tasso M20 device will be used to investigate the stability of blood samples obtained from the Tasso M-20 device containing immunosuppressive drugs Tacrolimus under the conditions of shipping

4. Stability of blood samples which contains immunosuppressive drug Tacrolimus under conditions of storage [up to 20 months]

   Blood specimens obtained by the Tasso M20 device will be used to investigate the stability of blood samples containing immunosuppressive drugs Tacrolimus under the conditions of storage

5. Stability of blood samples which contains immunosuppressive drug Sirolimus under conditions of storage [Oct 2021 up to 20 months]

   Blood specimens obtained from the Tasso device will be used to investigate the stability of blood samples containing immunosuppressive drugs Sirolimus under the conditions of storage

6. Stability of blood samples obtained which contains immunosuppressive drug Cyclosporin A under conditions of storage [up to 20 months]

   Blood specimens obtained from the Tasso M20 device will be used to investigate the stability of blood samples containing immunosuppressive drugs Cyclosporin A under the conditions of storage

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years to 18 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Males and females <18 years of age

2. Greater than 5 kg

3. Receiving one or more immunosuppressive drugs (CYA, TAC, and SIR) as the standard of care

4. Has scheduled/anticipated blood draw to quantify the concentration of the immunosuppressive drugs (CYA, TAC, and SIR) for clinical indications

5. Parental/guardian permission (informed consent), and subject's assent if applicable.

Exclusion Criteria:

1. Subjects who are not receiving one or more immunosuppressive drugs (CYA, TAC, and SIR) as the standard of care will be excluded from the study

2. Unable to provide blood samples.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital of Phildelphia	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

• Children's Hospital of Philadelphia

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

• Koster RA, Niemeijer P, Veenhof H, Hateren KV, Alffenaar JC, Touw DJ. A volumetric absorptive microsampling LC-MS/MS method for five immunosuppressants and their hematocrit effects. Bioanalysis. 2019 Mar;11(6):495-508. doi: 10.4155/bio-2018-0312. Epub 2019 Mar 20.
• Mbughuni MM, Stevens MA, Langman LJ, Kudva YC, Sanchez W, Dean PG, Jannetto PJ. Volumetric Microsampling of Capillary Blood Spot vs Whole Blood Sampling for Therapeutic Drug Monitoring of Tacrolimus and Cyclosporin A: Accuracy and Patient Satisfaction. J Appl Lab Med. 2020 May 1;5(3):516-530. doi: 10.1093/jalm/jfaa005.
• Roadcap B, Hussain A, Dreyer D, Carter K, Dube N, Xu Y, Anderson M, Berthier E, Vazvaei F, Bateman K, Woolf E. Clinical application of volumetric absorptive microsampling to the gefapixant development program. Bioanalysis. 2020 Jul;12(13):893-904. doi: 10.4155/bio-2020-0074. Epub 2020 Jul 10. Erratum in: Bioanalysis. 2021 Mar;13(5):409.

• Responsible Party: Children's Hospital of Philadelphia
• ClinicalTrials.gov Identifier: NCT04989686
• Other Study ID Numbers: 21-018761
• First Posted: Aug 4, 2021
• Last Update Posted: Mar 31, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Keywords provided by Children's Hospital of Philadelphia: microsampling; cyclosporine A; tacrolimus; sirolimus; Tasso-M20

Study Results

No Results Posted as of Mar 31, 2022