Short Stature, IdiopathicPhase 1NCT02412943
Pappalysin 2 (PAPP-A2) Enzyme Replacement
A Phase 1 study testing Fresh Frozen Plasma in people with Short Stature, Idiopathic, run by Children's Hospital Medical Center, Cincinnati at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Short Stature, Idiopathic
- What is being tested?
- Fresh Frozen Plasma
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2015to May 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Homozygous for a defect in PAPPA2.
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
About this study
Official title: 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.
Read the 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.
- Conditions
- Short Stature, Idiopathic
- Being tested
- Fresh Frozen Plasma
- Medical subject headings
- Dwarfism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fresh Frozen PlasmaOther
Liquid portion of human blood that was centrifuged, separated, and frozen solid within 6 hours of collection
| Study group | Role | What they receive |
|---|---|---|
| PAPP-A2 Enzyme Replacement | Experimental | A 20 cc/kg transfusion of Fresh Frozen Plasma will be given over 3 hours on day 0. Receives: Other: Fresh Frozen Plasma |
What is being measured
The primary outcome is the main question the study is designed to answer.
Decrease in IGF-1
Decrease in either total IGF-1 or IGFBP-3 of 20% or greater as a clinically meaningful decrease in levels
Measured: 5 minutes
Secondary outcomes (1)
Length of decrease in IGF-1
Measured: up to 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Apr 2015 (estimated)
- Study startApr 2015
- Primary completionMay 2015
- Study completionMay 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Short Stature, IdiopathicStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital Medical Center, Cincinnati
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Andrew Dauber, MD, Principal investigator, Children's Hospital Medical Center, Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02412943
- Sponsor's protocol ID
- PAPPA2 Replacement
- Status last verified
- May 2015
- First submitted
- 1 Apr 2015
- Last updated
- 28 May 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PAPP-A2 Enzyme Replacement Therapy Using Plasma Transfusion
- ClinicalTrials.gov ID
- NCT02412943
- Acronym / sponsor ID
- PAPPA2 Replacement
- Conditions
- Short Stature, Idiopathic
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Children's Hospital Medical Center, CincinnatiUniversity, hospital or other
- Study start
- Apr 2015
- Primary completion
- May 2015 (actual)
- Study completion
- May 2015 (actual)
- First posted
- 9 Apr 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| PAPP-A2 Enzyme Replacement | Experimental | Other: Fresh Frozen PlasmaA 20 cc/kg transfusion of Fresh Frozen Plasma will be given over 3 hours on day 0. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Homozygous for a defect in PAPPA2.
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Fresh Frozen PlasmaLiquid portion of human blood that was centrifuged, separated, and frozen solid within 6 hours of collection | Other | PAPP-A2 Enzyme Replacement |
Primary outcome
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
1 secondary outcome
Length of decrease in IGF-1
Time frame: up to 30 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 May 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andrew Dauber, MD principal investigator
Children's Hospital Medical Center, Cincinnati
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Fresh Frozen Plasma in people with Short Stature, Idiopathic, run by Children's Hospital Medical Center, Cincinnati at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 May 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Decrease in IGF-1 (time frame: 5 minutes). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 May 2015.