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Completed

NCT Number: NCT02412943

Pappalysin 2 (PAPP-A2) Enzyme Replacement

This study evaluates the transfusion of fresh frozen plasma containing the enzyme PAPP-A2 into the a female adult. This female adult has a mutated version of PAPP-A2 that prevents the unbinding of IGF-1 from IGF binding proteins. The investigator's hypothesize that transfusion of plasma with donor PAPP-A2 will lead to the unbinding of IGF-1 from its binding proteins and that they will be able to measure free IGF-1 in the blood of this female adult.

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Key information

Conditions

Short Stature, Idiopathic Bone Diseases Bone Diseases, Developmental Congenital, Hereditary, and Neonatal Diseases and Abnormalities Dwarfism Endocrine System Diseases Genetic Diseases, Inborn Musculoskeletal Diseases

Age range

18 year and older

Sex eligibility

Female

Study type

Interventional

Phase

Phase 1

Primary location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

About this study

PAPP-A2 is a plasma protease that is known to cleave IGFBP-3 and IGFBP-5. It is thought that this cleavage frees up IGF-1 from its bound form allowing it to become the active free IGF-1. The participant has short stature accompanied with elevated plasma levels of both IGF-1 and IGF binding protein 3 (IGFBP-3). Genetic analysis of the participant identified a novel missense mutation in PAPPA2 (Ala1033Val). This gene is a perfect candidate to explain our patients' phenotype. The investigators' hypothesis is that loss of activity of PAPP-A2 leads to an inability to cleave the IGF binding proteins and thus an overall elevation in IGFBP-3 and consequent elevation in total IGF-1. However, this IGF-1 cannot be freed up and is thus not able to be active leading to short stature. The patient's missense variant is predicted to be damaging by in silicon prediction models such as Polyphen2. Furthermore, two knock out mouse models of PAPPA2 as well as a zebrafish knock out exist, all showing growth retardation (post-natally in the mice). Taken together, this is definitive evidence that the patients' mutation in PAPPA2 is responsible for their short stature phenotype.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Homozygous for a defect in PAPPA2.

Exclusion criteria

None

Treatment and study plan

Fresh Frozen Plasma

Other

Liquid portion of human blood that was centrifuged, separated, and frozen solid within 6 hours of collection

Primary outcomes

  1. Decrease in IGF-1

    Time frame: 5 minutes

    Decrease in either total IGF-1 or IGFBP-3 of 20% or greater as a clinically meaningful decrease in levels

Secondary outcomes

  1. Length of decrease in IGF-1

    Time frame: up to 30 days

Sponsors and collaborators

Lead sponsor

Children's Hospital Medical Center, Cincinnati

Other

Registry information

Official study title

PAPP-A2 Enzyme Replacement Therapy Using Plasma Transfusion

Important dates

Study start
2015
Primary completion
2015
Study completion
2015
First posted
Apr 9, 2015
Registry last updated
May 28, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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