Plasminogen Activator Inhibitor-1 DeficiencyPhase 4NCT05317806
Metformin Use in Cardiac Fibrosis in PAI-1 Deficiency
A Phase 4 study testing Metformin Extended Release Oral Tablet in people with Plasminogen Activator Inhibitor-1 Deficiency and Cardiac Fibrosis, run by Indiana Hemophilia &Thrombosis Center, Inc. at 1 site in United States.
Trial summary
This study will evaluate the efficacy and safety of metformin, in patients 18-65 years of age with homozygous plasminogen activator inhibitor-1 (PAI-1) deficiency, with or without cardiac fibrosis, for a period of 60 months. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Plasminogen Activator Inhibitor-1 Deficiency, Cardiac Fibrosis
- What is being tested?
- Metformin Extended Release Oral Tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Oct 2022to Oct 2027
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Confirmed homozygosity for mutation in SERPINE-1 for PAI-1 deficiency
- Male or female
- Aged 18-65 years
- Willing and able to choose between being in a metformin Treatment group (daily metformin) or an Observation group (no study drug) at study entry
- Capable of understanding and willing to comply with the conditions of the study (in the opinion of the study investigator(s))
- Have read, understood and be able to provide written informed consent
Who cannot join
- Not homozygous for SERPINE-1 mutation for PAI-1 deficiency, based on genetic testing
- Ages <18 or >65 years
- Renal dysfunction (Cockcroft Gault CrCl < 30)
- History of hypersensitivity of metformin or any component in the extended release formulation
- Unwillingness to avoid alcohol
- Currently prescribed cimetidine, dolutegravir, patiromer, ranolazine, or tafenoquine and no alternate therapy is possible
Show all 11Show fewer
- History of illicit drug or alcohol abuse within 48 weeks prior to screening, in the study investigators' judgment
- Concomitant disease, condition, significant abnormality on screening evaluations or laboratory tests, or treatment that could interfere with the conduct of the study, or that would, in the opinion of the study investigator(s), pose an additional unacceptable risk in administering study drug to the patient
- Receipt of any other investigational medicinal product currently being administered (or planned to be administered)
- Inability to comply with the study protocol (in the opinion of the study investigator(s))
- Inability to understand and provide written informed consent
Trial locations and contacts
1 site in 1 country.
United States1 site
Indiana Hemophilia and Thrombosis Center
Indianapolis, Indiana, 46260
About this study
Official title: Use of Metformin in Prevention and Treatment of Cardiac Fibrosis in PAI-1 Deficient Population
This study will evaluate the efficacy and safety of metformin, in patients 18-65 years of age with homozygous plasminogen activator inhibitor-1 (PAI-1) deficiency, with or without cardiac fibrosis, for a period of 60 months. The starting dose of metformin will be 500 mg up to a maximum dose of 2000 mg for a period of 5 years with the aim to assess the safety and efficacy of metformin on prevention/stabilization or regression of cardiac fibrosis in a Treated population vs. a Comparison population.
Read the detailed description
This study is a phase 4, prospective, open-label, US single center study to assess the efficacy and safety of metformin for prevention or stabilization or regression of cardiac fibrosis in individuals homozygous for PAI-1 deficiency. Approximately 15 patients 18-65 years of age are expected to be enrolled, due to the rarity of this blood disorder. The study will have one metformin Treatment group (daily metformin administered) and one Observation group (no study drug administered). Subjects will be consented and screened by Indiana Hemophilia and Thrombosis Center (IHTC) staff. Individuals will be eligible for study participation if they meet all inclusion criteria. Subjects will be excluded from the study if they meet any of the exclusion criteria. US-labeled oral metformin (extended release) will be administered using the FDA-approved dosing regimen for diabetes mellitus type II starting at a dose of 500 mg and escalating up to a maximum of 2000 mg. In the final assessment, subjects who receive metformin for at least 36 months (and up to a maximum of 60 months) will be considered part of the Treated population. Subjects who refuse treatment with metformin or complete <36 months of treatment on metformin either due to intolerance to the study drug or due to any other reason, will be considered part of the Comparison population and will be followed clinically. Females will be offered the option to temporarily discontinue metformin during pregnancy and/or lactation period; they will be considered part of the Treated population if they receive metformin for at least 36 months during the study (those 36 months need not be consecutive). If they receive metformin for 0 to <36 months, they will be considered part of the Comparison population. The study enrollment period will be 12 months. Every subject will be in the study for a period of 60 months from the point of enrollment. There is no minimum on-study period. The decision to continue metformin treatment beyond the study period in the metformin Treatment group, will be made based on drug efficacy, patient tolerability/preference, and provider discretion.
Basic laboratory parameters (serum chemistry and hematology), specific cardiac markers (NT-pro BNP, TGF-β1) cardiac imaging and electrocardiograms will be performed at baseline, at study close out/subject withdrawal, and as specified in the schedule of activities. Adverse events (AE) will be recorded on an ongoing basis as they occur during the study. During the study, annual cardiac consultation, New York Heart Association (NYHA) scale and as needed, the Kansas City Cardiomyopathy Questionnaire (KCCQ-12) will be completed by patients.
The primary analysis will be performed when the last patient has completed 60 months in the study, is lost to follow up or has withdrawn from the study treatment, whichever occurs first.
An interim analysis will be performed at 30 months. All patients will be included in the interim analysis. This interim analysis will be performed for safety.
Definitions
- Complete PAI-1 deficiency defined as subjects with homozygous mutation in SERPINE 1.
During the clinical trial, subjects will be grouped according to whether they are currently receiving study drug or not. This will affect the schedule of study visits and assays/procedures performed.
- Metformin Treatment group: The group of individuals who are currently receiving metformin
- Observation group: The group of individuals who are NOT currently receiving metformin (this includes those who opted to never receive metformin) Patients will be allowed to switch between metformin treatment group and observation group.
Following the completion of the clinical trial, subjects will be grouped according to the total amount of time they received study drug. This grouping is for analytical/statistical purposes only.
- Treated population: Individuals who received at least 36 months of metformin treatment while on study
- Comparison population: Individuals who did not receive metformin treatment at any point during the study, or received metformin for a total less than 36 months of treatment while on study i.e. 0 to <36 months of treatment
- Being tested
- Metformin Extended Release Oral Tablet
- Keywords
- PAI-1 deficiency, Amish, cardiac fibrosis, Metformin
- Medical subject headings
- Plasminogen Activator Inhibitor-1 Deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Metformin Extended Release Oral TabletDrug
Also called Glucophage XR
daily metformin treatment vs. no treatment with metformin
| Study group | Role | What they receive |
|---|---|---|
| Metformin Treatment Group | Experimental | Subjects with PAI-1 deficiency with or without cardiac fibrosis, receiving daily treatment with metformin for a daily range of 500-2000mg Receives: Drug: Metformin Extended Release Oral Tablet |
| Observation Group | No intervention | Subjects with PAI-1 deficiency with or without cardiac fibrosis, not receiving treatment with metformin Subjects are allowed to switch between the two groups |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of individuals homozygous for PAI-1 deficiency with stable or improved cardiac fibrosis
Measured using cardiac MRI to quantify the percentage cardiac fibrosis.
Measured: through the study annually, up to 60 months
Number of individuals homozygous for PAI-1 deficiency with stable or improved Transforming growth factor (TGF-β1)
Measured by a blood draw as a surrogate marker for status of cardiac fibrosis stability or reduction.
Measured: through the study annually, up to 60 months
Secondary outcomes (5)
Number of individuals homozygous for PAI-1 deficiency with metformin related adverse events as assessed by grading of diarrhea (CTCAE v5.0)
Safety and tolerability of metformin when administered to individuals homozygous for PAI-1 deficiency as assessed by side effect profile (as measured by the type and number of adverse drug reactions and serious adverse drug reactions )
Measured: approximately monthly (±4 weeks) until maximum tolerated dose for metformin is achieved until 6 months (±4 weeks) and then every 3 months (±4 weeks) for the entire study period for the metformin group
Number of individuals homozygous for PAI-1 deficiency with clinical symptoms of heart failure as measured by the New York Heart Association (NYHA) scale and as needed, the Kansas City Cardiomyopathy Questionnaire (KCCQ-12)
Objective evaluation of cardiac symptoms by using a scale and questionnaire.
New York Heart Association (NYHA) scale: lowest scale is Functional capacity I, Objective assessment A; Highest scale is Functional capacity IV, Objective assessment D. Higher scores worst outcome.
Measured: 6 months after study enrollment, through the study annually, up to 60 months
Number of individuals homozygous for PAI-1 deficiency with additional signs of heart failure assessed by measuring N- terminal prohormone beta natriuretic peptide (NT-pro BNP)
Objective evaluation of heart failure using NT-proBNP value as stable, increasing or decreasing
Measured: through the study annually, up to 60 months
Number of individuals homozygous for PAI-1 deficiency with stable or improved ejection fraction on echocardiogram
Evaluate changes in ejection fraction by standard transthoracic echocardiogram
Measured: through the study annually, up to 60 months
Number of individuals homozygous for PAI-1 deficiency with clinical symptoms of heart failure impacting their health as measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ-12)
Objective evaluation of cardiac failure symptoms impact on health by using a questionnaire.
Kansas City Cardiomyopathy Questionnaire (KCCQ-12): KCCQ scores are scaled from 0 to 100 and frequently summarized in 25-point ranges, where scores represent health status as follows: 0 to 24: very poor to poor; 25 to 49: poor to fair; 50 to 74: fair to good; and 75 to 100: good to excellent. Higher scores are better outcome
Measured: 6 months after study enrollment, through the study annually, up to 60 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2022
- Study start10 Oct 2022
- Primary completionOct 2027 (estimated)
- Study completionOct 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (36)Papers the sponsor has linked to this study.
- Other trials for Plasminogen Activator Inhibitor-1 DeficiencyStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- The study will have one metformin Treatment group (daily metformin administered) and one Observation group (no study drug administered)
- Masking
- None (open label)
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Indiana Hemophilia &Thrombosis Center, Inc.
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Sweta Gupta, Indiana Hemophilia &Thrombosis Center, Inc.
- Investigators
- Sweta Gupta, MD, Principal investigator, Indiana Hemophilia and Thrombosis Center, IncMagdalena Lewandowska, MD, Principal investigator, Indiana Hemophilia and Thrombosis Center, IncAmy D Shapiro, MD, Study director, Indiana Hemophilia and Thrombosis Center, Inc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05317806
- Sponsor's protocol ID
- R2O210069
- Status last verified
- Oct 2024
- First submitted
- 8 Mar 2022
- Last updated
- 6 Nov 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: TBD based on analysis
Publications
Loskutoff DJ, Sawdey M, Mimuro J. Type 1 plasminogen activator inhibitor. Prog Hemost Thromb. 1989;9:87-115. No abstract available.
PubMed 2492381Chmielewska J, Ranby M, Wiman B. Evidence for a rapid inhibitor to tissue plasminogen activator in plasma. Thromb Res. 1983 Aug 1;31(3):427-36. doi: 10.1016/0049-3848(83)90407-3.
PubMed 20217999Chmielewska J, Ranby M, Wiman B. Kinetics of the inhibition of plasminogen activators by the plasminogen-activator inhibitor. Evidence for 'second-site' interactions. Biochem J. 1988 Apr 15;251(2):327-32. doi: 10.1042/bj2510327.
PubMed 3135797Mehta R, Shapiro AD. Plasminogen activator inhibitor type 1 deficiency. Haemophilia. 2008 Nov;14(6):1255-60. doi: 10.1111/j.1365-2516.2008.01834.x.
PubMed 19141166Fay WP, Parker AC, Condrey LR, Shapiro AD. Human plasminogen activator inhibitor-1 (PAI-1) deficiency: characterization of a large kindred with a null mutation in the PAI-1 gene. Blood. 1997 Jul 1;90(1):204-8.
PubMed 9207454Fay WP, Shapiro AD, Shih JL, Schleef RR, Ginsburg D. Brief report: complete deficiency of plasminogen-activator inhibitor type 1 due to a frame-shift mutation. N Engl J Med. 1992 Dec 10;327(24):1729-33. doi: 10.1056/NEJM199212103272406. No abstract available.
PubMed 1435917Iwaki T, Tanaka A, Miyawaki Y, Suzuki A, Kobayashi T, Takamatsu J, Matsushita T, Umemura K, Urano T, Kojima T, Terao T, Kanayama N. Life-threatening hemorrhage and prolonged wound healing are remarkable phenotypes manifested by complete plasminogen activator inhibitor-1 deficiency in humans. J Thromb Haemost. 2011 Jun;9(6):1200-6. doi: 10.1111/j.1538-7836.2011.04288.x.
PubMed 21486382Iwaki T, Nagahashi K, Kobayashi T, Umemura K, Terao T, Kanayama N. The first report of uncontrollable subchorionic and retroplacental haemorrhage inducing preterm labour in complete PAI-1 deficiency in a human. Thromb Res. 2012 Apr;129(4):e161-3. doi: 10.1016/j.thromres.2011.10.008. Epub 2011 Nov 17. No abstract available.
PubMed 22099705Iwaki T, Nagahashi K, Takano K, Suzuki-Inoue K, Kanayama N, Umemura K, Urano T. Mutation in a highly conserved glycine residue in strand 5B of plasminogen activator inhibitor 1 causes polymerisation. Thromb Haemost. 2017 May 3;117(5):860-869. doi: 10.1160/TH16-07-0572. Epub 2017 Feb 23.
PubMed 28229167Angleton P, Chandler WL, Schmer G. Diurnal variation of tissue-type plasminogen activator and its rapid inhibitor (PAI-1). Circulation. 1989 Jan;79(1):101-6. doi: 10.1161/01.cir.79.1.101.
PubMed 2491971Heiman M, Gupta S, Shapiro AD. The obstetric, gynaecological and fertility implications of homozygous PAI-1 deficiency: single-centre experience. Haemophilia. 2014 May;20(3):407-12. doi: 10.1111/hae.12313. Epub 2013 Nov 22.
PubMed 24261743Flevaris P, Vaughan D. The Role of Plasminogen Activator Inhibitor Type-1 in Fibrosis. Semin Thromb Hemost. 2017 Mar;43(2):169-177. doi: 10.1055/s-0036-1586228. Epub 2016 Aug 24.
PubMed 27556351Ghosh AK, Vaughan DE. PAI-1 in tissue fibrosis. J Cell Physiol. 2012 Feb;227(2):493-507. doi: 10.1002/jcp.22783.
PubMed 21465481Ghosh AK, Bradham WS, Gleaves LA, De Taeye B, Murphy SB, Covington JW, Vaughan DE. Genetic deficiency of plasminogen activator inhibitor-1 promotes cardiac fibrosis in aged mice: involvement of constitutive transforming growth factor-beta signaling and endothelial-to-mesenchymal transition. Circulation. 2010 Sep 21;122(12):1200-9. doi: 10.1161/CIRCULATIONAHA.110.955245. Epub 2010 Sep 7.
PubMed 20823384Xu Z, Castellino FJ, Ploplis VA. Plasminogen activator inhibitor-1 (PAI-1) is cardioprotective in mice by maintaining microvascular integrity and cardiac architecture. Blood. 2010 Mar 11;115(10):2038-47. doi: 10.1182/blood-2009-09-244962. Epub 2009 Dec 15.
PubMed 20009036
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Use of Metformin in Prevention and Treatment of Cardiac Fibrosis in PAI-1 Deficient Population
- ClinicalTrials.gov ID
- NCT05317806
- Acronym / sponsor ID
- R2O210069
- Keywords
- PAI-1 deficiency, Amish, cardiac fibrosis, Metformin
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- Indiana Hemophilia &Thrombosis Center, Inc.University, hospital or other
- Study start
- 10 Oct 2022 (actual)
- Primary completion
- Oct 2027 (estimated)
- Study completion
- Oct 2027 (estimated)
- First posted
- 8 Apr 2022 (actual)
- 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 will evaluate the efficacy and safety of metformin, in patients 18-65 years of age with homozygous plasminogen activator inhibitor-1 (PAI-1) deficiency, with or without cardiac fibrosis, for a period of 60 months. The starting dose of metformin will be 500 mg up to a maximum dose of 2000 mg for a period of 5 years with the aim to assess the safety and efficacy of metformin on prevention/stabilization or regression of cardiac fibrosis in a Treated population vs. a Comparison population.
Detailed description
This study is a phase 4, prospective, open-label, US single center study to assess the efficacy and safety of metformin for prevention or stabilization or regression of cardiac fibrosis in individuals homozygous for PAI-1 deficiency. Approximately 15 patients 18-65 years of age are expected to be enrolled, due to the rarity of this blood disorder. The study will have one metformin Treatment group (daily metformin administered) and one Observation group (no study drug administered). Subjects will be consented and screened by Indiana Hemophilia and Thrombosis Center (IHTC) staff. Individuals will be eligible for study participation if they meet all inclusion criteria. Subjects will be excluded from the study if they meet any of the exclusion criteria. US-labeled oral metformin (extended release) will be administered using the FDA-approved dosing regimen for diabetes mellitus type II starting at a dose of 500 mg and escalating up to a maximum of 2000 mg. In the final assessment, subjects who receive metformin for at least 36 months (and up to a maximum of 60 months) will be considered part of the Treated population. Subjects who refuse treatment with metformin or complete <36 months of treatment on metformin either due to intolerance to the study drug or due to any other reason, will be considered part of the Comparison population and will be followed clinically. Females will be offered the option to temporarily discontinue metformin during pregnancy and/or lactation period; they will be considered part of the Treated population if they receive metformin for at least 36 months during the study (those 36 months need not be consecutive). If they receive metformin for 0 to <36 months, they will be considered part of the Comparison population. The study enrollment period will be 12 months. Every subject will be in the study for a period of 60 months from the point of enrollment. There is no minimum on-study period. The decision to continue metformin treatment beyond the study period in the metformin Treatment group, will be made based on drug efficacy, patient tolerability/preference, and provider discretion.
Basic laboratory parameters (serum chemistry and hematology), specific cardiac markers (NT-pro BNP, TGF-β1) cardiac imaging and electrocardiograms will be performed at baseline, at study close out/subject withdrawal, and as specified in the schedule of activities. Adverse events (AE) will be recorded on an ongoing basis as they occur during the study. During the study, annual cardiac consultation, New York Heart Association (NYHA) scale and as needed, the Kansas City Cardiomyopathy Questionnaire (KCCQ-12) will be completed by patients.
The primary analysis will be performed when the last patient has completed 60 months in the study, is lost to follow up or has withdrawn from the study treatment, whichever occurs first.
An interim analysis will be performed at 30 months. All patients will be included in the interim analysis. This interim analysis will be performed for safety.
Definitions
- Complete PAI-1 deficiency defined as subjects with homozygous mutation in SERPINE 1.
During the clinical trial, subjects will be grouped according to whether they are currently receiving study drug or not. This will affect the schedule of study visits and assays/procedures performed.
- Metformin Treatment group: The group of individuals who are currently receiving metformin
- Observation group: The group of individuals who are NOT currently receiving metformin (this includes those who opted to never receive metformin) Patients will be allowed to switch between metformin treatment group and observation group.
Following the completion of the clinical trial, subjects will be grouped according to the total amount of time they received study drug. This grouping is for analytical/statistical purposes only.
- Treated population: Individuals who received at least 36 months of metformin treatment while on study
- Comparison population: Individuals who did not receive metformin treatment at any point during the study, or received metformin for a total less than 36 months of treatment while on study i.e. 0 to <36 months of treatment
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- The study will have one metformin Treatment group (daily metformin administered) and one Observation group (no study drug administered)
| Arm | Type | Receives |
|---|---|---|
| Metformin Treatment Group | Experimental | Drug: Metformin Extended Release Oral TabletSubjects with PAI-1 deficiency with or without cardiac fibrosis, receiving daily treatment with metformin for a daily range of 500-2000mg |
| Observation Group | No intervention | –Subjects with PAI-1 deficiency with or without cardiac fibrosis, not receiving treatment with metformin Subjects are allowed to switch between the two groups |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Confirmed homozygosity for mutation in SERPINE-1 for PAI-1 deficiency
- Male or female
- Aged 18-65 years
- Willing and able to choose between being in a metformin Treatment group (daily metformin) or an Observation group (no study drug) at study entry
- Capable of understanding and willing to comply with the conditions of the study (in the opinion of the study investigator(s))
Key exclusion criteria (11 listed)
- Not homozygous for SERPINE-1 mutation for PAI-1 deficiency, based on genetic testing
- Ages <18 or >65 years
- Renal dysfunction (Cockcroft Gault CrCl < 30)
- History of hypersensitivity of metformin or any component in the extended release formulation
- Unwillingness to avoid alcohol
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 |
|---|---|---|
| Metformin Extended Release Oral TabletAlso: Glucophage XRdaily metformin treatment vs. no treatment with metformin | Drug | Metformin Treatment Group |
Primary outcome
Number of individuals homozygous for PAI-1 deficiency with stable or improved cardiac fibrosis
Time frame: through the study annually, up to 60 months
Measured using cardiac MRI to quantify the percentage cardiac fibrosis.
Number of individuals homozygous for PAI-1 deficiency with stable or improved Transforming growth factor (TGF-β1)
Time frame: through the study annually, up to 60 months
Measured by a blood draw as a surrogate marker for status of cardiac fibrosis stability or reduction.
5 secondary outcomes
Number of individuals homozygous for PAI-1 deficiency with metformin related adverse events as assessed by grading of diarrhea (CTCAE v5.0)
Time frame: approximately monthly (±4 weeks) until maximum tolerated dose for metformin is achieved until 6 months (±4 weeks) and then every 3 months (±4 weeks) for the entire study period for the metformin group
Number of individuals homozygous for PAI-1 deficiency with clinical symptoms of heart failure as measured by the New York Heart Association (NYHA) scale and as needed, the Kansas City Cardiomyopathy Questionnaire (KCCQ-12)
Time frame: 6 months after study enrollment, through the study annually, up to 60 months
Number of individuals homozygous for PAI-1 deficiency with additional signs of heart failure assessed by measuring N- terminal prohormone beta natriuretic peptide (NT-pro BNP)
Time frame: through the study annually, up to 60 months
Number of individuals homozygous for PAI-1 deficiency with stable or improved ejection fraction on echocardiogram
Time frame: through the study annually, up to 60 months
Number of individuals homozygous for PAI-1 deficiency with clinical symptoms of heart failure impacting their health as measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ-12)
Time frame: 6 months after study enrollment, through the study annually, up to 60 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2024.
- Background: PubMed 2492381Loskutoff DJ, Sawdey M, Mimuro J. Type 1 plasminogen activator inhibitor. Prog Hemost Thromb. 1989;9:87-115. No abstract available.
- Background: PubMed 20217999Chmielewska J, Ranby M, Wiman B. Evidence for a rapid inhibitor to tissue plasminogen activator in plasma. Thromb Res. 1983 Aug 1;31(3):427-36. doi: 10.1016/0049-3848(83)90407-3.
- Background: PubMed 3135797Chmielewska J, Ranby M, Wiman B. Kinetics of the inhibition of plasminogen activators by the plasminogen-activator inhibitor. Evidence for 'second-site' interactions. Biochem J. 1988 Apr 15;251(2):327-32. doi: 10.1042/bj2510327.
- Background: PubMed 19141166Mehta R, Shapiro AD. Plasminogen activator inhibitor type 1 deficiency. Haemophilia. 2008 Nov;14(6):1255-60. doi: 10.1111/j.1365-2516.2008.01834.x.
- Background: PubMed 9207454Fay WP, Parker AC, Condrey LR, Shapiro AD. Human plasminogen activator inhibitor-1 (PAI-1) deficiency: characterization of a large kindred with a null mutation in the PAI-1 gene. Blood. 1997 Jul 1;90(1):204-8.
- Background: PubMed 1435917Fay WP, Shapiro AD, Shih JL, Schleef RR, Ginsburg D. Brief report: complete deficiency of plasminogen-activator inhibitor type 1 due to a frame-shift mutation. N Engl J Med. 1992 Dec 10;327(24):1729-33. doi: 10.1056/NEJM199212103272406. No abstract available.
- Background: PubMed 21486382Iwaki T, Tanaka A, Miyawaki Y, Suzuki A, Kobayashi T, Takamatsu J, Matsushita T, Umemura K, Urano T, Kojima T, Terao T, Kanayama N. Life-threatening hemorrhage and prolonged wound healing are remarkable phenotypes manifested by complete plasminogen activator inhibitor-1 deficiency in humans. J Thromb Haemost. 2011 Jun;9(6):1200-6. doi: 10.1111/j.1538-7836.2011.04288.x.
- Background: PubMed 22099705Iwaki T, Nagahashi K, Kobayashi T, Umemura K, Terao T, Kanayama N. The first report of uncontrollable subchorionic and retroplacental haemorrhage inducing preterm labour in complete PAI-1 deficiency in a human. Thromb Res. 2012 Apr;129(4):e161-3. doi: 10.1016/j.thromres.2011.10.008. Epub 2011 Nov 17. No abstract available.
- Background: PubMed 28229167Iwaki T, Nagahashi K, Takano K, Suzuki-Inoue K, Kanayama N, Umemura K, Urano T. Mutation in a highly conserved glycine residue in strand 5B of plasminogen activator inhibitor 1 causes polymerisation. Thromb Haemost. 2017 May 3;117(5):860-869. doi: 10.1160/TH16-07-0572. Epub 2017 Feb 23.
- Background: PubMed 2491971Angleton P, Chandler WL, Schmer G. Diurnal variation of tissue-type plasminogen activator and its rapid inhibitor (PAI-1). Circulation. 1989 Jan;79(1):101-6. doi: 10.1161/01.cir.79.1.101.
- Background: PubMed 24261743Heiman M, Gupta S, Shapiro AD. The obstetric, gynaecological and fertility implications of homozygous PAI-1 deficiency: single-centre experience. Haemophilia. 2014 May;20(3):407-12. doi: 10.1111/hae.12313. Epub 2013 Nov 22.
- Background: PubMed 27556351Flevaris P, Vaughan D. The Role of Plasminogen Activator Inhibitor Type-1 in Fibrosis. Semin Thromb Hemost. 2017 Mar;43(2):169-177. doi: 10.1055/s-0036-1586228. Epub 2016 Aug 24.
- Gupta S, Sealls W, Shapiro A. Rare coagulation disorders resource room - plasminogen activator inbitor type 1 deficiency. Rare coagulation disorders resource room \[cited August 8, 2019\]Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. TBD based on analysis
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.
Sweta Gupta, MD principal investigator
Indiana Hemophilia and Thrombosis Center, Inc
Magdalena Lewandowska, MD principal investigator
Indiana Hemophilia and Thrombosis Center, Inc
Amy D Shapiro, MD study director
Indiana Hemophilia and Thrombosis Center, Inc
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Metformin Extended Release Oral Tablet in people with Plasminogen Activator Inhibitor-1 Deficiency and Cardiac Fibrosis, run by Indiana Hemophilia &Thrombosis Center, Inc. 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 6 inclusion and 11 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: under way, not looking for participants, as of the sponsor's last update on 6 Nov 2024. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
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?
Number of individuals homozygous for PAI-1 deficiency with stable or improved cardiac fibrosis (time frame: through the study annually, up to 60 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05317806, which also lists 36 linked publications.
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 6 Nov 2024.