Microsampling Assays for Immunosuppressive Drugs in Children

Immunosuppression Clinical Trial

— MAIDEN  

Official title:

Microsampling Assays for Immunosuppressive Drugs in Children

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04989686
• Other study ID #: 22-020410
• Secondary ID: 5R21HD106103-02
• Status: Recruiting
• Start date: June 8, 2023
• Est. completion date: June 2024

Study information

• Verified date: December 2023
• Source: Children's Hospital of Philadelphia
• Contact: Kevin J Downes, MD
• Phone: 215-590-4024
• Email: downeskj[@]chop.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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 device, called Tasso-M20, to the traditional way of collecting blood from a vein. Additionally Investigators are interested in assessing patient and family perceptions of the Tasso-M20 device being used for immunosuppressive therapy and their comfortability using the device outside of a clinical setting.

The primary objective of this project is to identify the relationship between cyclosporine A (CYA), tacrolimus (TAC), and sirolimus (SIR) concentrations in the venous blood (gold-standard) and capillary whole blood obtained using the microsampling device Tasso-M20.

The secondary objective of this study is to investigate the stability of CYA, TAC, and SIR in blood samples collected using the Tasso-M20 device under the conditions of shipping and storage.

The sub-study objective is to thematically compare subjects' and families' perceptions of blood collection via the Tasso-M20 device and standard venous blood collection.

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 (17.5 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.

Children and their parents/guardians who consent to the optional sub-study will be administered a brief survey after one study visit, to ask about their perceptions of the two methods of blood collection that they experienced at the visit.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: June 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 17 Years

Eligibility

Inclusion Criteria:

1. Males and females <18 years of age

2. Weight greater than 5 kg

3. Receiving CYA, TAC, and/or SIR as standard of care

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

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

Exclusion Criteria:

1) Unable to provide blood samples.

• Potential subjects and their parents/guardians may be approached prior to having a blood draw scheduled if they meet all other eligibility criteria.

Sub-Study Criteria:

Sub-study criteria for child participants will not differ from the main study. Adult participants are required to be a parent/legal guardian of a study subject.

Related Conditions & MeSH terms

• Immunosuppression

Intervention

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.

Locations

Country	Name	City	State
United States	Children's Hospital of Phildelphia	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Children's Hospital of Philadelphia	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Country where clinical trial is conducted

United States, 

References & Publications (24)

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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. — View Citation

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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. — View Citation

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* Note: There are 24 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Usability of the two methods of blood collection	Usability will be measured by assessing participants survey responses about their perceptions of blood collection methods they experienced	up to 20 months
Other	Acceptability of the two methods of blood collection	Acceptability will be measured by assessing participants survey responses about their perceptions of blood collection methods they experienced	up to 20 months
Primary	Clinical validation of microsampling assay of Tacrolimus	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.	up to 20 months
Primary	Clinical validation of microsampling assay of Sirolimus	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.	up to 20 months
Primary	Clinical validation of microsampling assay of Cyclosporine A	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.	up to 20 months
Secondary	Stability of blood samples which contains immunosuppressive drug Tacrolimus under conditions of shipping	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	up to 20 months
Secondary	Stability of blood samples obtained which contains immunosuppressive drug Sirolimus under conditions of shipping	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	up to 20 months
Secondary	Stability of blood samples containing immunosuppressive drug Cyclosporine A under conditions of shipping	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	up to 20 months
Secondary	Stability of blood samples which contains immunosuppressive drug Tacrolimus under conditions of storage	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	up to 20 months
Secondary	Stability of blood samples which contains immunosuppressive drug Sirolimus under conditions of storage	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	up to 20 months
Secondary	Stability of blood samples obtained which contains immunosuppressive drug Cyclosporine A under conditions of storage	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	up to 20 months