Acute Coronary SyndromeNCT04993664
Influence of Pelacarsen on Patients After Myocardial Infarction With High Lp(a) Values (PEMILA)
A study testing Pelacarsen (TQJ230) in people with Acute Coronary Syndrome and Lipoproteinemia, run by University Medical Centre Ljubljana at 1 site in Slovenia.
Trial summary
The aim of study is to examine the relationship between lipid subfractions, inflammation and structural-functional properties of the arterial wall in patients after myocardial infarction with high lipoprotein (a) (Lp (a)) levels, to study genetic polymorphisms that determine lipid subfractions concentration on the… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Acute Coronary Syndrome, Lipoproteinemia, Inflammation
- What is being tested?
- Pelacarsen (TQJ230)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteSlovenia
- Study dates
- 1 Oct 2021to 1 Oct 2022
- Phase
- Interventional
- 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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- concentration Lp (a) above 700 mg / L,
- optimally treated risk factors for cardiovascular events according to currently valid guidelines,
- history of myocardial infarction having occurred in the period 3 months to 10 years prior to the screening visit and / or
- history of ischemic stroke having occurred in the period 3 months to 10 years prior to the screening visit and / or
- clinically significant symptomatic peripheral artery disease.
Who cannot join
- uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg and / or diastolic blood pressure ≥ 100 mmHg),
- heart failure New York Heart Association (NYHA) class IV,
- history of malignancy of any organ system,
- history of hemorrhagic stroke or other major bleeding,
- platelet count <140,000 per mm3,
- active liver disease or hepatic dysfunction (elevated transaminases above 3 times the norm, elevated bilirubin above 2 times the norm, elevated creatinine kinase above 3 times the norm),
Show all 10Show fewer
- significant kidney disease (oGFR <30 ml / min),
- pregnant or nursing women,
- life expectancy less than 5 years,
- unwillingness to participate or lack of availability for follow-up.
Trial locations and contacts
1 site in 1 country.
Slovenia1 site
University Medical Centre Ljubljana-Department of Vascular diseases and dept. of Cardiology
Ljubljana, 1000
About this study
Official title: Influence of Pelacarsen on Arterial Wall Properties and Risk Factors in Patients After Myocardial Infarction With High Lp(a) Values
The aim of study is to examine the relationship between lipid subfractions, inflammation and structural-functional properties of the arterial wall in patients after myocardial infarction with high lipoprotein (a) (Lp (a)) levels, to study genetic polymorphisms that determine lipid subfractions concentration on the functional and morphological properties of the arterial vascular wall in patients after myocardial infarction with high Lp (a) levels, to study the effect of pelacarsen on lipid subfractions, inflammation and structural-functional properties of arterial wall in patients after myocardial infarction with high Lp (a) levels and to study the influence of NOS-3 gene expression on the functional and morphological properties of the arterial vascular wall in the same patients.
Impaired blood fat metabolism and chronic inflammation represent possible causes of atherosclerosis. Lp (a) is an independent risk factor for cardiovascular disease and a prognostic predictor in patients after myocardial infarction. Despite recommended screening for elevated Lp (a), there is no specific drug treatment approved to reduce cardiovascular risk through lowering Lp (a). Besides subtilisin-kexin convertase type 9 (PCSK9) inhibitors, antisense oligonucleotides (ASOs) are currently only therapeutic agents that significantly reduce serum Lp (a) concentration. Pelacarsen by using an ASO directed against the messenger ribonucleic acid (mRNA) of apolipoprotein (a), reduces the production of apolipoprotein (a) in the liver and thus, the level of Lp (a).
However, there are no data on the relationship between Lp (a) values and polymorphisms for Lp (a), indicators of inflammation and impaired arterial function, and response to treatment with pelacarsen in patients after myocardial infarction with extremely high Lp (a) levels.
Read the detailed description
Impaired blood fat metabolism and chronic inflammation represent possible causes of atherosclerosis. The early stage of the atherosclerosis process is characterized by endothelial cell damage, which results in impaired release and function of nitric oxide (NO) from the endothelium. NO is formed by endothelial NO synthetase (NOS-3) from the amino acid L-arginine, which is most pronounced in the vascular wall and is also most important in the process of atherosclerosis. The NOS-3 gene is located on chromosome 7; in the region 7q35-7q36. Functional polymorphisms are those that alter the expression or activity of NOS-3. Among functional polymorphisms, rs2070744, rs3918226 and rs1799983 single nucleotide polymorphisms (SNP) are important. Variations in the NOS-3 genes cause diversity in NO bioavailability and are responsible for endothelial dysfunction.
Lipoprotein (a) (Lp (a)) is a specific subfraction of lipoprotein that is an independent risk factor for cardiovascular disease and predicts the residual risk in patients with pre-existing atherosclerosis, regardless of serum LDL-cholesterol concentration. Circulating levels of Lp(a) are mainly genetically determined and varies according to ethnic group. Lp(a) has atherosclerotic, prothrombotic and pro-inflammatory effects. The gene encoding apo (a); LPA, is located on the long arm of chromosome 6 (6q2,6-2,7) and most variants in Lp (a) can be explained by genetic diversity in LPA. To date, the most studied genetic variant is the Kringle-IV type-2 (KIV2) polymorphism, which explains 30-70% of the diversity in Lp (a) in the population. Some KIV2 replicates are associated with smaller isoforms and higher plasma concentrations of Lp (a) which are causally and independently associated with coronary heart disease. Within LPA, the number of KIV2 copies, as well as one nucleotide polymorphism (SNP), rs3798220 and rs10455872, are associated with Lp (a) concentration and coronary heart disease. Besides subtilisin-kexin convertase type 9 (PCSK9) inhibitors, antisense oligonucleotides (ASOs) are currently only therapeutic agents that significantly reduce serum Lp (a) concentration and that have shown effectiveness in clinical trials, to provide reductions in cardiovascular morbidity and mortality. Pelacarsen by using an ASO directed against the mRNA of apolipoprotein (a), reduces the production of apolipoprotein (a) in the liver and thus, the level of Lp (a).
A 6-month randomized, double-blind, parallel group and placebo-controlled study will include 60 patients with established cardiovascular disease (CVD) (including myocardial infarction, ischemic stroke or symptomatic peripheral artery disease) and Lp (a) levels above 700 mg / L.
The investigators will do anamnesis, targeted clinical examination, take blood samples for laboratory measurements, ultrasound measure endothelium-dependent dilatation of the brachial artery and beta stiffness of carotid arteries. Patients will be divided into two groups according to the randomization list. The first group will receive pelacarsen 80 mg subcutaneously and the second group will receive corresponding placebo. After 6 months, the investigators will repeat all the mentioned investigations. Patients will be informed about the purpose and course of the study before starting the study. All patients will participate voluntarily, without pressure or inappropriate instigation and will give consent by signing the consent form.
The investigators hypotheses that in patients after myocardial infarction and high levels of Lp (a), Lp (a) and Lp (a) polymorphisms are associated with indicators of inflammation and structural-functional properties of the arterial wall; in patients after myocardial infarction and extremely high levels of Lp (a), pelacarsen reduces the value of Lp (a), indicators of inflammation and structural and functional involvement of the arterial wall; in patients after myocardial infarction and extremely high levels of Lp (a), the influence of pelacarsen on Lp (a), indicators of inflammation and structural-functional properties of the arterial wall depends on the presence of specific polymorphisms for Lp (a).
- Being tested
- Pelacarsen (TQJ230), Placebo
- Keywords
- Coronary heart disease, Acute coronary syndrome, Lipoprotein (a), Genetics, Secondary prevention, Endothelium, Inflammation, Genetic polymorphisms, NO synthetase, Dyslipidemia
- Medical subject headings
- Acute Coronary Syndrome, Inflammation, Coronary Disease, Dyslipidemias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pelacarsen (TQJ230)Drug
The first group will receive pelacarsen. Blood samples from all patients will be drawn for laboratory measurements and genetics determination. Ultrasound measurement of endothelium-dependent dilatation of the brachial artery and beta stiffness of carotid arteries will be measured.
PlaceboDrug
The second group will receive placebo. Blood samples from all patients will be drawn for laboratory measurements and genetics determination. Ultrasound measurement of endothelium-dependent dilatation of the brachial artery and beta stiffness of carotid arteries will be measured.
| Study group | Role | What they receive |
|---|---|---|
| Pelacarsen group (TQJ230) | Experimental | The first group will receive 80 mg of pelacarsen every month subcutaneously for 6 months. Receives: Drug: Pelacarsen (TQJ230) |
| Placebo group | Placebo comparator | The first group will receive 80 mg of placebo every month subcutaneously for 6 months. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ultrasound functional and morphological properties of the arterial wall and Lp (a) concentration
Functional and morphological characteristics of arterial wall will correlate to Lp (a) concentrations.
Measured: Baseline
Concentration of Lp (a) and SNP in the LPA gene
The serum concentration of Lp (a) will correlate with single nucleotide polymorphisms (SNP) in the LPA gene.
Measured: Baseline
The effect of pelacarsen on functional and morphological properties of arterial wall after 6 months
Pelacarsen will improve functional and morphological properties of arterial wall. The investigators expect the improvements will be in correlation with the decrease of Lp (a) concentration.
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Aug 2021
- Study start1 Oct 2021 (estimated)
- Primary completion30 Jun 2022 (estimated)
- Study completion1 Oct 2022 (estimated)
Why it stopped: Administrative reason
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 Acute Coronary SyndromeStudies of the same condition, open and under way.
- More trials run by University Medical Centre LjubljanaThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Medical Centre Ljubljana
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Miran Sebestjen, University Medical Centre Ljubljana
- Investigators
- Miran Šebeštjen, prof., PhD, Study chair, University Medical Centre Ljubljana (Slovenia)Sabina Ugovšek, MD, Principal investigator, University Medical Centre Ljubljana (Slovenia)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04993664
- Sponsor's protocol ID
- PEMILA
- Status last verified
- Dec 2021
- First submitted
- 30 Jul 2021
- Last updated
- 3 Jan 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Pagidipati NJ, Gaziano TA. Estimating deaths from cardiovascular disease: a review of global methodologies of mortality measurement. Circulation. 2013 Feb 12;127(6):749-56. doi: 10.1161/CIRCULATIONAHA.112.128413. No abstract available.
PubMed 23401116McGill HC Jr, McMahan CA, Herderick EE, Malcom GT, Tracy RE, Strong JP. Origin of atherosclerosis in childhood and adolescence. Am J Clin Nutr. 2000 Nov;72(5 Suppl):1307S-1315S. doi: 10.1093/ajcn/72.5.1307s.
PubMed 11063473Wang JC, Bennett M. Aging and atherosclerosis: mechanisms, functional consequences, and potential therapeutics for cellular senescence. Circ Res. 2012 Jul 6;111(2):245-59. doi: 10.1161/CIRCRESAHA.111.261388.
PubMed 22773427Egashira K. Clinical importance of endothelial function in arteriosclerosis and ischemic heart disease. Circ J. 2002 Jun;66(6):529-33. doi: 10.1253/circj.66.529.
PubMed 12074266Bisoendial RJ, Kastelein JJ, Stroes ES. C-reactive protein and atherogenesis: from fatty streak to clinical event. Atherosclerosis. 2007 Dec;195(2):e10-8. doi: 10.1016/j.atherosclerosis.2007.04.053. Epub 2007 Jul 31.
PubMed 17669411Giles TD, Sander GE, Nossaman BD, Kadowitz PJ. Impaired vasodilation in the pathogenesis of hypertension: focus on nitric oxide, endothelial-derived hyperpolarizing factors, and prostaglandins. J Clin Hypertens (Greenwich). 2012 Apr;14(4):198-205. doi: 10.1111/j.1751-7176.2012.00606.x.
PubMed 22458740Tada H, Takamura M, Kawashiri MA. Lipoprotein(a) as an Old and New Causal Risk Factor of Atherosclerotic Cardiovascular Disease. J Atheroscler Thromb. 2019 Jul 1;26(7):583-591. doi: 10.5551/jat.RV17034. Epub 2019 Apr 30.
PubMed 31061262Machado-Silva W, Alfinito-Kreis R, Carvalho LS, Quinaglia-E-Silva JC, Almeida OL, Brito CJ, Ferreira AP, Cordova C, Sposito AC, Nobrega OT; Brasilia Heart Study Group. Endothelial nitric oxide synthase genotypes modulate peripheral vasodilatory properties after myocardial infarction. Gene. 2015 Sep 1;568(2):165-9. doi: 10.1016/j.gene.2015.05.042. Epub 2015 May 20.
PubMed 26002446Marsden PA, Heng HH, Scherer SW, Stewart RJ, Hall AV, Shi XM, Tsui LC, Schappert KT. Structure and chromosomal localization of the human constitutive endothelial nitric oxide synthase gene. J Biol Chem. 1993 Aug 15;268(23):17478-88.
PubMed 7688726Oliveira-Paula GH, Lacchini R, Tanus-Santos JE. Endothelial nitric oxide synthase: From biochemistry and gene structure to clinical implications of NOS3 polymorphisms. Gene. 2016 Jan 10;575(2 Pt 3):584-99. doi: 10.1016/j.gene.2015.09.061. Epub 2015 Sep 28.
PubMed 26428312Hingorani AD, Liang CF, Fatibene J, Lyon A, Monteith S, Parsons A, Haydock S, Hopper RV, Stephens NG, O'Shaughnessy KM, Brown MJ. A common variant of the endothelial nitric oxide synthase (Glu298-->Asp) is a major risk factor for coronary artery disease in the UK. Circulation. 1999 Oct 5;100(14):1515-20. doi: 10.1161/01.cir.100.14.1515.
PubMed 10510054Bostom AG, Cupples LA, Jenner JL, Ordovas JM, Seman LJ, Wilson PW, Schaefer EJ, Castelli WP. Elevated plasma lipoprotein(a) and coronary heart disease in men aged 55 years and younger. A prospective study. JAMA. 1996 Aug 21;276(7):544-8. doi: 10.1001/jama.1996.03540070040028.
PubMed 8709403Schaefer EJ, Lamon-Fava S, Jenner JL, McNamara JR, Ordovas JM, Davis CE, Abolafia JM, Lippel K, Levy RI. Lipoprotein(a) levels and risk of coronary heart disease in men. The lipid Research Clinics Coronary Primary Prevention Trial. JAMA. 1994 Apr 6;271(13):999-1003. doi: 10.1001/jama.1994.03510370051031.
PubMed 8139085Willeit P, Ridker PM, Nestel PJ, Simes J, Tonkin AM, Pedersen TR, Schwartz GG, Olsson AG, Colhoun HM, Kronenberg F, Drechsler C, Wanner C, Mora S, Lesogor A, Tsimikas S. Baseline and on-statin treatment lipoprotein(a) levels for prediction of cardiovascular events: individual patient-data meta-analysis of statin outcome trials. Lancet. 2018 Oct 13;392(10155):1311-1320. doi: 10.1016/S0140-6736(18)31652-0. Epub 2018 Oct 4.
PubMed 30293769Berthold HK, Gouni-Berthold I. Hyperlipoproteinemia(a): clinical significance and treatment options. Atheroscler Suppl. 2013 Jan;14(1):1-5. doi: 10.1016/j.atherosclerosissup.2012.10.037.
PubMed 23357133
Study at a glance
From the registry record, last updated by the sponsor on 3 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Influence of Pelacarsen on Arterial Wall Properties and Risk Factors in Patients After Myocardial Infarction With High Lp(a) Values
- ClinicalTrials.gov ID
- NCT04993664
- Acronym / sponsor ID
- PEMILA
- Keywords
- Coronary heart disease, Acute coronary syndrome, Lipoprotein (a), Genetics, Secondary prevention, Endothelium, Inflammation, Genetic polymorphisms
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Administrative reason
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University Medical Centre LjubljanaUniversity, hospital or other
- Study start
- 1 Oct 2021 (estimated)
- Primary completion
- 30 Jun 2022 (estimated)
- Study completion
- 1 Oct 2022 (estimated)
- First posted
- 6 Aug 2021 (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.
The aim of study is to examine the relationship between lipid subfractions, inflammation and structural-functional properties of the arterial wall in patients after myocardial infarction with high lipoprotein (a) (Lp (a)) levels, to study genetic polymorphisms that determine lipid subfractions concentration on the functional and morphological properties of the arterial vascular wall in patients after myocardial infarction with high Lp (a) levels, to study the effect of pelacarsen on lipid subfractions, inflammation and structural-functional properties of arterial wall in patients after myocardial infarction with high Lp (a) levels and to study the influence of NOS-3 gene expression on the functional and morphological properties of the arterial vascular wall in the same patients.
Impaired blood fat metabolism and chronic inflammation represent possible causes of atherosclerosis. Lp (a) is an independent risk factor for cardiovascular disease and a prognostic predictor in patients after myocardial infarction. Despite recommended screening for elevated Lp (a), there is no specific drug treatment approved to reduce cardiovascular risk through lowering Lp (a). Besides subtilisin-kexin convertase type 9 (PCSK9) inhibitors, antisense oligonucleotides (ASOs) are currently only therapeutic agents that significantly reduce serum Lp (a) concentration. Pelacarsen by using an ASO directed against the messenger ribonucleic acid (mRNA) of apolipoprotein (a), reduces the production of apolipoprotein (a) in the liver and thus, the level of Lp (a).
However, there are no data on the relationship between Lp (a) values and polymorphisms for Lp (a), indicators of inflammation and impaired arterial function, and response to treatment with pelacarsen in patients after myocardial infarction with extremely high Lp (a) levels.
Detailed description
Impaired blood fat metabolism and chronic inflammation represent possible causes of atherosclerosis. The early stage of the atherosclerosis process is characterized by endothelial cell damage, which results in impaired release and function of nitric oxide (NO) from the endothelium. NO is formed by endothelial NO synthetase (NOS-3) from the amino acid L-arginine, which is most pronounced in the vascular wall and is also most important in the process of atherosclerosis. The NOS-3 gene is located on chromosome 7; in the region 7q35-7q36. Functional polymorphisms are those that alter the expression or activity of NOS-3. Among functional polymorphisms, rs2070744, rs3918226 and rs1799983 single nucleotide polymorphisms (SNP) are important. Variations in the NOS-3 genes cause diversity in NO bioavailability and are responsible for endothelial dysfunction.
Lipoprotein (a) (Lp (a)) is a specific subfraction of lipoprotein that is an independent risk factor for cardiovascular disease and predicts the residual risk in patients with pre-existing atherosclerosis, regardless of serum LDL-cholesterol concentration. Circulating levels of Lp(a) are mainly genetically determined and varies according to ethnic group. Lp(a) has atherosclerotic, prothrombotic and pro-inflammatory effects. The gene encoding apo (a); LPA, is located on the long arm of chromosome 6 (6q2,6-2,7) and most variants in Lp (a) can be explained by genetic diversity in LPA. To date, the most studied genetic variant is the Kringle-IV type-2 (KIV2) polymorphism, which explains 30-70% of the diversity in Lp (a) in the population. Some KIV2 replicates are associated with smaller isoforms and higher plasma concentrations of Lp (a) which are causally and independently associated with coronary heart disease. Within LPA, the number of KIV2 copies, as well as one nucleotide polymorphism (SNP), rs3798220 and rs10455872, are associated with Lp (a) concentration and coronary heart disease. Besides subtilisin-kexin convertase type 9 (PCSK9) inhibitors, antisense oligonucleotides (ASOs) are currently only therapeutic agents that significantly reduce serum Lp (a) concentration and that have shown effectiveness in clinical trials, to provide reductions in cardiovascular morbidity and mortality. Pelacarsen by using an ASO directed against the mRNA of apolipoprotein (a), reduces the production of apolipoprotein (a) in the liver and thus, the level of Lp (a).
A 6-month randomized, double-blind, parallel group and placebo-controlled study will include 60 patients with established cardiovascular disease (CVD) (including myocardial infarction, ischemic stroke or symptomatic peripheral artery disease) and Lp (a) levels above 700 mg / L.
The investigators will do anamnesis, targeted clinical examination, take blood samples for laboratory measurements, ultrasound measure endothelium-dependent dilatation of the brachial artery and beta stiffness of carotid arteries. Patients will be divided into two groups according to the randomization list. The first group will receive pelacarsen 80 mg subcutaneously and the second group will receive corresponding placebo. After 6 months, the investigators will repeat all the mentioned investigations. Patients will be informed about the purpose and course of the study before starting the study. All patients will participate voluntarily, without pressure or inappropriate instigation and will give consent by signing the consent form.
The investigators hypotheses that in patients after myocardial infarction and high levels of Lp (a), Lp (a) and Lp (a) polymorphisms are associated with indicators of inflammation and structural-functional properties of the arterial wall; in patients after myocardial infarction and extremely high levels of Lp (a), pelacarsen reduces the value of Lp (a), indicators of inflammation and structural and functional involvement of the arterial wall; in patients after myocardial infarction and extremely high levels of Lp (a), the influence of pelacarsen on Lp (a), indicators of inflammation and structural-functional properties of the arterial wall depends on the presence of specific polymorphisms for Lp (a).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pelacarsen group (TQJ230) | Experimental | Drug: Pelacarsen (TQJ230)The first group will receive 80 mg of pelacarsen every month subcutaneously for 6 months. |
| Placebo group | Placebo comparator | Drug: PlaceboThe first group will receive 80 mg of placebo every month subcutaneously for 6 months. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- concentration Lp (a) above 700 mg / L,
- optimally treated risk factors for cardiovascular events according to currently valid guidelines,
- history of myocardial infarction having occurred in the period 3 months to 10 years prior to the screening visit and / or
- history of ischemic stroke having occurred in the period 3 months to 10 years prior to the screening visit and / or
- clinically significant symptomatic peripheral artery disease.
Key exclusion criteria (10 listed)
- uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg and / or diastolic blood pressure ≥ 100 mmHg),
- heart failure New York Heart Association (NYHA) class IV,
- history of malignancy of any organ system,
- history of hemorrhagic stroke or other major bleeding,
- platelet count <140,000 per mm3,
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 |
|---|---|---|
| Pelacarsen (TQJ230)The first group will receive pelacarsen. Blood samples from all patients will be drawn for laboratory measurements and genetics determination. Ultrasound measurement of endothelium-dependent dilatation of the brachial artery and beta stiffness of carotid arteries will be measured. | Drug | Pelacarsen group (TQJ230) |
| PlaceboThe second group will receive placebo. Blood samples from all patients will be drawn for laboratory measurements and genetics determination. Ultrasound measurement of endothelium-dependent dilatation of the brachial artery and beta stiffness of carotid arteries will be measured. | Drug | Placebo group |
Primary outcome
Ultrasound functional and morphological properties of the arterial wall and Lp (a) concentration
Time frame: Baseline
Functional and morphological characteristics of arterial wall will correlate to Lp (a) concentrations.
Concentration of Lp (a) and SNP in the LPA gene
Time frame: Baseline
The serum concentration of Lp (a) will correlate with single nucleotide polymorphisms (SNP) in the LPA gene.
The effect of pelacarsen on functional and morphological properties of arterial wall after 6 months
Time frame: Baseline
Pelacarsen will improve functional and morphological properties of arterial wall. The investigators expect the improvements will be in correlation with the decrease of Lp (a) concentration.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jan 2022.
- Background: PubMed 23401116Pagidipati NJ, Gaziano TA. Estimating deaths from cardiovascular disease: a review of global methodologies of mortality measurement. Circulation. 2013 Feb 12;127(6):749-56. doi: 10.1161/CIRCULATIONAHA.112.128413. No abstract available.
- Background: PubMed 11063473McGill HC Jr, McMahan CA, Herderick EE, Malcom GT, Tracy RE, Strong JP. Origin of atherosclerosis in childhood and adolescence. Am J Clin Nutr. 2000 Nov;72(5 Suppl):1307S-1315S. doi: 10.1093/ajcn/72.5.1307s.
- Background: PubMed 22773427Wang JC, Bennett M. Aging and atherosclerosis: mechanisms, functional consequences, and potential therapeutics for cellular senescence. Circ Res. 2012 Jul 6;111(2):245-59. doi: 10.1161/CIRCRESAHA.111.261388.
- Background: PubMed 12074266Egashira K. Clinical importance of endothelial function in arteriosclerosis and ischemic heart disease. Circ J. 2002 Jun;66(6):529-33. doi: 10.1253/circj.66.529.
- Background: PubMed 17669411Bisoendial RJ, Kastelein JJ, Stroes ES. C-reactive protein and atherogenesis: from fatty streak to clinical event. Atherosclerosis. 2007 Dec;195(2):e10-8. doi: 10.1016/j.atherosclerosis.2007.04.053. Epub 2007 Jul 31.
- Background: PubMed 22458740Giles TD, Sander GE, Nossaman BD, Kadowitz PJ. Impaired vasodilation in the pathogenesis of hypertension: focus on nitric oxide, endothelial-derived hyperpolarizing factors, and prostaglandins. J Clin Hypertens (Greenwich). 2012 Apr;14(4):198-205. doi: 10.1111/j.1751-7176.2012.00606.x.
- Background: PubMed 31061262Tada H, Takamura M, Kawashiri MA. Lipoprotein(a) as an Old and New Causal Risk Factor of Atherosclerotic Cardiovascular Disease. J Atheroscler Thromb. 2019 Jul 1;26(7):583-591. doi: 10.5551/jat.RV17034. Epub 2019 Apr 30.
- Background: PubMed 26002446Machado-Silva W, Alfinito-Kreis R, Carvalho LS, Quinaglia-E-Silva JC, Almeida OL, Brito CJ, Ferreira AP, Cordova C, Sposito AC, Nobrega OT; Brasilia Heart Study Group. Endothelial nitric oxide synthase genotypes modulate peripheral vasodilatory properties after myocardial infarction. Gene. 2015 Sep 1;568(2):165-9. doi: 10.1016/j.gene.2015.05.042. Epub 2015 May 20.
- Background: PubMed 7688726Marsden PA, Heng HH, Scherer SW, Stewart RJ, Hall AV, Shi XM, Tsui LC, Schappert KT. Structure and chromosomal localization of the human constitutive endothelial nitric oxide synthase gene. J Biol Chem. 1993 Aug 15;268(23):17478-88.
- Background: PubMed 26428312Oliveira-Paula GH, Lacchini R, Tanus-Santos JE. Endothelial nitric oxide synthase: From biochemistry and gene structure to clinical implications of NOS3 polymorphisms. Gene. 2016 Jan 10;575(2 Pt 3):584-99. doi: 10.1016/j.gene.2015.09.061. Epub 2015 Sep 28.
- Background: PubMed 10510054Hingorani AD, Liang CF, Fatibene J, Lyon A, Monteith S, Parsons A, Haydock S, Hopper RV, Stephens NG, O'Shaughnessy KM, Brown MJ. A common variant of the endothelial nitric oxide synthase (Glu298-->Asp) is a major risk factor for coronary artery disease in the UK. Circulation. 1999 Oct 5;100(14):1515-20. doi: 10.1161/01.cir.100.14.1515.
- Background: PubMed 8709403Bostom AG, Cupples LA, Jenner JL, Ordovas JM, Seman LJ, Wilson PW, Schaefer EJ, Castelli WP. Elevated plasma lipoprotein(a) and coronary heart disease in men aged 55 years and younger. A prospective study. JAMA. 1996 Aug 21;276(7):544-8. doi: 10.1001/jama.1996.03540070040028.
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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.
Miran Šebeštjen, prof., PhD study chair
University Medical Centre Ljubljana (Slovenia)
Sabina Ugovšek, MD principal investigator
University Medical Centre Ljubljana (Slovenia)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Pelacarsen (TQJ230) in people with Acute Coronary Syndrome and Lipoproteinemia, run by University Medical Centre Ljubljana at 1 site in Slovenia.
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 5 inclusion and 10 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: withdrawn, as of the sponsor's last update on 3 Jan 2022. 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 Slovenia. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
Ultrasound functional and morphological properties of the arterial wall and Lp (a) concentration (time frame: Baseline). The study lists 3 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 NCT04993664, 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 3 Jan 2022.