Clinical trial NCT04319081: Study to Evaluate Changes in Cognitive Function in Patients Treated With PCSK9 Inhibitors
Official title: Multicenter, Observational and Prospective Study to Evaluate Changes in Cognitive Function in Patients Treated With PCSK9 Inhibitors (MEMOGAL)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cognitive Function
Hypercholesterolemia
Quality of Life
Keywords: Cognitive Function
Hypercholesterolemia
Quality of Life
Pharmacoeconomics
PCSK9 inhibitors
Alirocumab
Evolocumab
Lead sponsor: Hospital Clinico Universitario de Santiago
Sponsor class: OTHER
First posted: 2020-03-24
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients diagnosed with familial hypercholesterolemia (homozygous and heterozygous) and/or cardiovascular disease with LDL-cholestrol value \> 100 mg/dL and maximum statine doses or intolerance. With a first prescription of PCSK9 inhibitors

Brief summary: The main objective will be to evaluate the changes in the cognitive function in naive patients treated with PCSK9 inhibitors (Alirocumab and Evolocumab) by using the Montreal Cognitive Assesment questionnaire (MOCA).

The secondary objectives will be: 1) To evaluate the levels of LDL-cholesterol changes from the beginning to the end of the study 2) To evaluate changes in Quality of Life among the EuroQol EQ-5D-3L questionnaire (it will also be associated to the cognitive function) 3) Assesment of direct costs in medications and outpatients consultations related with the health procedures.


Eligibility criteria: Inclusion Criteria:

* Patients 18 years old or over
* To start with the first funded dose of PCSK9 inhibitors ( LDL \> 100 mg/dL)
* Maximum dose or statin intolerance

Exclusion Criteria:

* Diagnosis of any disease related with cognitive deterioration

Primary outcomes:
measure: Changes in cognitive function
timeFrame: 24 to 36 months
Secondary outcomes:
measure: LDL-cholesterol values
timeFrame: 24 to 36 months
measure: Changes in Quality of life
timeFrame: 24 to 36 months
measure: Direct costs
timeFrame: 24 to 36 months
Other outcomes:
measure: Total Cholesterol
timeFrame: 24 to 36 months
measure: Lp(a)
timeFrame: 24 to 36 months
measure: Cost-effectiveness
timeFrame: 24 to 36 months
Locations:
city: Cee
country: Spain
facility: Hospital de Virxen da Xunqueira de Cee
state: A Coruña
city: Ferrol
country: Spain
facility: Hospital Arquiteto Marcide de Ferrol
state: A Coruña
city: Ribeira
country: Spain
facility: Hospital del Barbanza
state: A Coruña
city: Santiago De Compostela
country: Spain
facility: Hospital Clínico Universitario de Santiago de Compostela
state: A Coruña
city: Burela
country: Spain
facility: Hospital Público da Mariña de Burela
state: Lugo
city: Monforte De Lemos
country: Spain
facility: Hospital de Monforte
state: Lugo
city: O Barco De Valdeorras
country: Spain
facility: Hospital do Barco de Valdeorras
state: Ourense
city: Vigo
country: Spain
facility: Hospital Alvaro Cunqueiro de Vigo
state: Pontevedra
city: A Coruña
country: Spain
facility: Complejo Hospitalario Universitario de A Coruña
city: Lugo
country: Spain
facility: Hospital Lucus-Augusti de Lugo
city: Ourense
country: Spain
facility: Complejo Hospitalario Universitario de Ourense
city: Pontevedra
country: Spain
facility: Complexo Hospitalario Universitario de Pontevedra
Study officials:
References:
citation: Giugliano RP, Mach F, Zavitz K, Kurtz C, Im K, Kanevsky E, Schneider J, Wang H, Keech A, Pedersen TR, Sabatine MS, Sever PS, Robinson JG, Honarpour N, Wasserman SM, Ott BR; EBBINGHAUS Investigators. Cognitive Function in a Randomized Trial of Evolocumab. N Engl J Med. 2017 Aug 17;377(7):633-643. doi: 10.1056/NEJMoa1701131.
citation: Schwartz GG, Steg PG, Szarek M, Bhatt DL, Bittner VA, Diaz R, Edelberg JM, Goodman SG, Hanotin C, Harrington RA, Jukema JW, Lecorps G, Mahaffey KW, Moryusef A, Pordy R, Quintero K, Roe MT, Sasiela WJ, Tamby JF, Tricoci P, White HD, Zeiher AM; ODYSSEY OUTCOMES Committees and Investigators. Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome. N Engl J Med. 2018 Nov 29;379(22):2097-2107. doi: 10.1056/NEJMoa1801174. Epub 2018 Nov 7.
citation: Sabatine MS, Giugliano RP, Keech AC, Honarpour N, Wiviott SD, Murphy SA, Kuder JF, Wang H, Liu T, Wasserman SM, Sever PS, Pedersen TR; FOURIER Steering Committee and Investigators. Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease. N Engl J Med. 2017 May 4;376(18):1713-1722. doi: 10.1056/NEJMoa1615664. Epub 2017 Mar 17.
citation: Kolodziejczak M, Navarese EP. Role of PCSK9 antibodies in cardiovascular disease: Critical considerations of mortality and neurocognitive findings from the current literature. Atherosclerosis. 2016 Apr;247:189-92. doi: 10.1016/j.atherosclerosis.2016.02.011. Epub 2016 Feb 15.
citation: Lipinski MJ, Benedetto U, Escarcega RO, Biondi-Zoccai G, Lhermusier T, Baker NC, Torguson R, Brewer HB Jr, Waksman R. The impact of proprotein convertase subtilisin-kexin type 9 serine protease inhibitors on lipid levels and outcomes in patients with primary hypercholesterolaemia: a network meta-analysis. Eur Heart J. 2016 Feb 7;37(6):536-45. doi: 10.1093/eurheartj/ehv563. Epub 2015 Nov 17.
citation: Shibata N, Ohnuma T, Higashi S, Higashi M, Usui C, Ohkubo T, Watanabe T, Kawashima R, Kitajima A, Ueki A, Nagao M, Arai H. No genetic association between PCSK9 polymorphisms and Alzheimer's disease and plasma cholesterol level in Japanese patients. Psychiatr Genet. 2005 Dec;15(4):239. doi: 10.1097/00041444-200512000-00004. No abstract available.
citation: Xue-Shan Z, Juan P, Qi W, Zhong R, Li-Hong P, Zhi-Han T, Zhi-Sheng J, Gui-Xue W, Lu-Shan L. Imbalanced cholesterol metabolism in Alzheimer's disease. Clin Chim Acta. 2016 May 1;456:107-114. doi: 10.1016/j.cca.2016.02.024. Epub 2016 Mar 2.
citation: Banach M, Rizzo M, Nikolic D, Howard G, Howard V, Mikhailidis D. Intensive LDL-cholesterol lowering therapy and neurocognitive function. Pharmacol Ther. 2017 Feb;170:181-191. doi: 10.1016/j.pharmthera.2016.11.001. Epub 2016 Nov 16.
citation: Paquette M, Saavedra YGL, Poirier J, Theroux L, Dea D, Baass A, Dufour R. Loss-of-Function PCSK9 Mutations Are Not Associated With Alzheimer Disease. J Geriatr Psychiatry Neurol. 2018 Mar;31(2):90-96. doi: 10.1177/0891988718764330. Epub 2018 Mar 21.
citation: Robinson JG, Rosenson RS, Farnier M, Chaudhari U, Sasiela WJ, Merlet L, Miller K, Kastelein JJ. Safety of Very Low Low-Density Lipoprotein Cholesterol Levels With Alirocumab: Pooled Data From Randomized Trials. J Am Coll Cardiol. 2017 Feb 7;69(5):471-482. doi: 10.1016/j.jacc.2016.11.037.
citation: Seijas-Amigo J, Rodriguez-Penas D, Estany-Gestal A, Suarez-Artime P, Santamaria-Cadavid M, Gonzalez-Juanatey JR. Observational multicentre prospective study to assess changes in cognitive function in patients treated with PCSK9i. Study protocol. Farm Hosp. 2021 Mar 5;45(3):150-154. doi: 10.7399/fh.11569.
citation: Seijas-Amigo J, Gayoso-Rey M, Mauriz-Montero MJ, Suarez-Artime P, Casas-Martinez A, Dominguez-Guerra M, Gonzalez-Freire L, Estany-Gestal A, Codero-Fort A, Rodriguez-Manero M, Gonzalez-Juanatey JR; e investigadores MEMOGAL. Impact of the COVID-19 pandemic in the lipid control of the patients that start PCSK9 inhibitors. Clin Investig Arterioscler. 2022 Sep-Oct;34(5):245-252. doi: 10.1016/j.arteri.2022.01.003. Epub 2022 Feb 3. English, Spanish.