- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02412943
Pappalysin 2 (PAPP-A2) Enzyme Replacement
May 27, 2015 updated by: Children's Hospital Medical Center, Cincinnati
PAPP-A2 Enzyme Replacement Therapy Using Plasma Transfusion
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
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.
Study Type
Interventional
Enrollment (Actual)
1
Phase
- Phase 1
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
-
-
Ohio
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Cincinnati, Ohio, United States, 45229
- Cincinnati Children's Hospital Medical Center
-
-
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
Female
Description
Inclusion Criteria:
- Homozygous for a defect in PAPPA2.
Exclusion Criteria: None
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: Basic Science
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: PAPP-A2 Enzyme Replacement
A 20 cc/kg transfusion of Fresh Frozen Plasma will be given over 3 hours on day 0.
|
Liquid portion of human blood that was centrifuged, separated, and frozen solid within 6 hours of collection
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
5 minutes
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Length of decrease in IGF-1
Time Frame: up to 30 days
|
up to 30 days
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: Andrew Dauber, MD, Children's Hospital Medical Center, Cincinnati
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, 2015
Primary Completion (Actual)
May 1, 2015
Study Completion (Actual)
May 1, 2015
Study Registration Dates
First Submitted
April 1, 2015
First Submitted That Met QC Criteria
April 8, 2015
First Posted (Estimate)
April 9, 2015
Study Record Updates
Last Update Posted (Estimate)
May 28, 2015
Last Update Submitted That Met QC Criteria
May 27, 2015
Last Verified
May 1, 2015
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- PAPPA2 Replacement
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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