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Cardiovascular disease remains the most pressing healthcare issue for developed countries and is becoming so for developing countries. There are a number of chronic therapies available for long-term management of risk. Short term therapies for subjects with an acute event, such as an episode of acute coronary syndrome (ACS), are focused on reperfusion and removing thrombus but most subsequent events are caused by atherosclerotic plaque rupture at a different site. There are no approved therapies that can rapidly reduce the burden of unstable, inflamed plaque in the overall coronary vascular bed. HDL has multiple actions that could lead to atherosclerotic plaque stabilization, such as rapid removal of large quantities of cholesterol from the vasculature, improvement in endothelial function, protection against oxidative damage and reduction in inflammation. This study will assess the effects of CER-001, an ApoA-I-based HDL mimetic, on indices of atherosclerotic plaque progression and regression as assessed by intravascular ultrasound (IVUS) measurements in patients with (ACS).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator |
| |
| Low Dose | Experimental | CER-001 Low Dose |
|
| Mid Dose | Experimental | CER-001 Mid Dose |
|
| High Dose | Experimental | CER-001 High Dose |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo | Drug | Weekly injection |
| |
| CER-001 |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Total Plaque Volume | Absolute change in total plaque volume, as assessed by IVUS, from the baseline measurement to the follow-up taken ~3 weeks following the final dose of study medication (approximately 9 weeks after the baseline assessment) | Baseline and 3 weeks post final dose |
| Measure | Description | Time Frame |
|---|---|---|
| Percent Change in Plaque Volume | Percent change in total plaque volume, as assessed by IVUS, from the baseline measurement to the follow-up taken ~3 weeks following the final dose of study medication (approximately 9 weeks after the baseline assessment) | Baseline and 3 weeks post final dose |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jean-Claude Tardif, MD | Montreal Heart Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Heart Center Research LLC | Huntsville | Alabama | 35801 | United States | ||
| Mayo Clinic - Arizona |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 10195926 | Background | Nanjee MN, Doran JE, Lerch PG, Miller NE. Acute effects of intravenous infusion of ApoA1/phosphatidylcholine discs on plasma lipoproteins in humans. Arterioscler Thromb Vasc Biol. 1999 Apr;19(4):979-89. doi: 10.1161/01.atv.19.4.979. | |
| 10441095 | Background | Eriksson M, Carlson LA, Miettinen TA, Angelin B. Stimulation of fecal steroid excretion after infusion of recombinant proapolipoprotein A-I. Potential reverse cholesterol transport in humans. Circulation. 1999 Aug 10;100(6):594-8. doi: 10.1161/01.cir.100.6.594. |
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| Drug |
Weekly injection |
|
| Phoenix |
| Arizona |
| 85054 |
| United States |
| VA San Diego Health Care Center | San Diego | California | 92161 | United States |
| Palm Beach Heart Institute, LLC - Zasa Clinical Research | Boynton Beach | Florida | 33472 | United States |
| Heart and Vascular Institute of Florida | Clearwater | Florida | 33755 | United States |
| Jacksonville Center for Clinical Research | Jacksonville | Florida | 32216 | United States |
| Saint Joseph Research Institute | Atlanta | Georgia | 30342 | United States |
| The Care Group, LLC | Indianapolis | Indiana | 46260 | United States |
| Suburban Hospital | Bethesda | Maryland | 20814 | United States |
| University of Michigan Health System | Ann Arbor | Michigan | 48109 | United States |
| Detroit Medical Center (DMC) Cardiovascular Institute | Detroit | Michigan | 48201 | United States |
| Cardiac and Vascular Research Center of Northern Michigan | Petoskey | Michigan | 49770 | United States |
| Alegent Research Center | Omaha | Nebraska | 68124 | United States |
| Buffalo Heart Group | Buffalo | New York | 14215 | United States |
| Buffalo Cardiology & Pulmonary Associates | Williamsville | New York | 14221 | United States |
| University of North Carolina Medical Center | Chapel Hill | North Carolina | 27599 | United States |
| LeBauer Cardiovascular Research Foundation | Greensboro | North Carolina | 27401 | United States |
| Sanford Heart Center | Fargo | North Dakota | 58122 | United States |
| South Oklahoma Heart Research | Oklahoma City | Oklahoma | 73135 | United States |
| Penn Presbyterian Medical Center | Philadelphia | Pennsylvania | 19104 | United States |
| Sanford Research / USD | Sioux Falls | South Dakota | 57104 | United States |
| Baptist Memorial Hospital | Memphis | Tennessee | 38120 | United States |
| Dallas VA Medical Center | Dallas | Texas | 75016 | United States |
| MultiCare Health System Research Institute / Cardiac Study Center | Tacoma | Washington | 98405 | United States |
| Foothills Medical Centre | Calgary | Alberta | T2N 2T9 | Canada |
| Victoria Heart Institute Foundation | Victoria | British Columbia | V8R 4R2 | Canada |
| St. John Health Center | St. John's | Newfoundland and Labrador | A1B 3V6 | Canada |
| London Health Sciences Center | London | Ontario | N6A 5A5 | Canada |
| St. Michael's Hospital | Toronto | Ontario | M5B 1W8 | Canada |
| Centre de Santé et de Services Sociaux de Laval | Laval | Quebec | H7M 3L9 | Canada |
| Montreal Heart Institute | Montreal | Quebec | H1T1C8 | Canada |
| Montreal General Hospital Research Institute | Montreal | Quebec | H3G 1A4 | Canada |
| Institut Universitaire de Cardiologie et Pneumologie de Québec (IUCPQ) | Québec | Quebec | G1V 4G5 | Canada |
| CSSS du Nord de Lanaudière | Saint-Charles-Borromée | Quebec | J6E 6J2 | Canada |
| Centre Hospitalier Régional de Trois-Rivières | Trois-Rivières | Quebec | G8Z 3R9 | Canada |
| Hôpital Cardiologique du Haut-Lévesque | Bordeaux | Pessac Cedex | 33064 | France |
| Clinique Pasteur | Toulouse | 31076 | France |
| Centre Hospitalier Universitaire de Toulouse Rangueil | Toulouse | France |
| Onze Lieve Vrouwe Gasthius | Amsterdam | AC | 1091 | Netherlands |
| Medisch Centrum Leeuwarden | Leeuwarden | AD | 8934 | Netherlands |
| Medisch Centrum Alkmaar | Alkmaar | Amsterdam | JD 1815 | Netherlands |
| Academic Medical Center | Amsterdam | AZ | 1105 | Netherlands |
| St. Antonius Ziekenhuis Nieuwegein | Nieuwegein | CM | 3430 | Netherlands |
| Maassstadziekenhuis Cardiology Research | Rotterdam | DZ | 3079 | Netherlands |
| Catharina Ziekenhuis Eindhoven | Eindhoven | EJ | 5623 | Netherlands |
| Medisch Spectrum Twente | Enschede | ER | 7513 | Netherlands |
| Canisius Wilhelmina Ziekenhuis | Nijmegen | SZ | 6532 | Netherlands |
| 11914243 | Background | Spieker LE, Sudano I, Hurlimann D, Lerch PG, Lang MG, Binggeli C, Corti R, Ruschitzka F, Luscher TF, Noll G. High-density lipoprotein restores endothelial function in hypercholesterolemic men. Circulation. 2002 Mar 26;105(12):1399-402. doi: 10.1161/01.cir.0000013424.28206.8f. |
| 18389214 | Background | Nieuwdorp M, Vergeer M, Bisoendial RJ, op 't Roodt J, Levels H, Birjmohun RS, Kuivenhoven JA, Basser R, Rabelink TJ, Kastelein JJ, Stroes ES. Reconstituted HDL infusion restores endothelial function in patients with type 2 diabetes mellitus. Diabetologia. 2008 Jun;51(6):1081-4. doi: 10.1007/s00125-008-0975-2. Epub 2008 Apr 4. No abstract available. |
| 19349317 | Background | Drew BG, Duffy SJ, Formosa MF, Natoli AK, Henstridge DC, Penfold SA, Thomas WG, Mukhamedova N, de Courten B, Forbes JM, Yap FY, Kaye DM, van Hall G, Febbraio MA, Kemp BE, Sviridov D, Steinberg GR, Kingwell BA. High-density lipoprotein modulates glucose metabolism in patients with type 2 diabetes mellitus. Circulation. 2009 Apr 21;119(15):2103-11. doi: 10.1161/CIRCULATIONAHA.108.843219. Epub 2009 Apr 6. |
| 18832751 | Background | Shaw JA, Bobik A, Murphy A, Kanellakis P, Blombery P, Mukhamedova N, Woollard K, Lyon S, Sviridov D, Dart AM. Infusion of reconstituted high-density lipoprotein leads to acute changes in human atherosclerotic plaque. Circ Res. 2008 Nov 7;103(10):1084-91. doi: 10.1161/CIRCRESAHA.108.182063. Epub 2008 Oct 2. |
| 20538165 | Background | Waksman R, Torguson R, Kent KM, Pichard AD, Suddath WO, Satler LF, Martin BD, Perlman TJ, Maltais JA, Weissman NJ, Fitzgerald PJ, Brewer HB Jr. A first-in-man, randomized, placebo-controlled study to evaluate the safety and feasibility of autologous delipidated high-density lipoprotein plasma infusions in patients with acute coronary syndrome. J Am Coll Cardiol. 2010 Jun 15;55(24):2727-35. doi: 10.1016/j.jacc.2009.12.067. |
| 17387133 | Background | Tardif JC, Gregoire J, L'Allier PL, Ibrahim R, Lesperance J, Heinonen TM, Kouz S, Berry C, Basser R, Lavoie MA, Guertin MC, Rodes-Cabau J; Effect of rHDL on Atherosclerosis-Safety and Efficacy (ERASE) Investigators. Effects of reconstituted high-density lipoprotein infusions on coronary atherosclerosis: a randomized controlled trial. JAMA. 2007 Apr 18;297(15):1675-82. doi: 10.1001/jama.297.15.jpc70004. Epub 2007 Mar 26. |
| 14600188 | Background | Nissen SE, Tsunoda T, Tuzcu EM, Schoenhagen P, Cooper CJ, Yasin M, Eaton GM, Lauer MA, Sheldon WS, Grines CL, Halpern S, Crowe T, Blankenship JC, Kerensky R. Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial. JAMA. 2003 Nov 5;290(17):2292-300. doi: 10.1001/jama.290.17.2292. |
| 24780501 | Derived | Tardif JC, Ballantyne CM, Barter P, Dasseux JL, Fayad ZA, Guertin MC, Kastelein JJ, Keyserling C, Klepp H, Koenig W, L'Allier PL, Lesperance J, Luscher TF, Paolini JF, Tawakol A, Waters DD; Can HDL Infusions Significantly QUicken Atherosclerosis REgression (CHI-SQUARE) Investigators. Effects of the high-density lipoprotein mimetic agent CER-001 on coronary atherosclerosis in patients with acute coronary syndromes: a randomized trial. Eur Heart J. 2014 Dec 7;35(46):3277-86. doi: 10.1093/eurheartj/ehu171. Epub 2014 Apr 29. |
| ID | Term |
|---|---|
| D054058 | Acute Coronary Syndrome |
| ID | Term |
|---|---|
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D014652 | Vascular Diseases |
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| ID | Term |
|---|---|
| C000591544 | CER-001 |
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