Clinical trial NCT03470376: NUtraceutical TReatment for hYpercholesterolemia in HIV-infected Patients
Official title: Lipid-lowering and Vascular Effects of a Nutraceutical Combination in HIV-infected Patients on Stable Antiretroviral Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hypercholesterolemia
Inflammation
Atherosclerosis
Keywords: cholesterol
nutraceutical
HIV
PCSK9
hsCRP
stiffness
Lead sponsor: University Of Perugia
Sponsor class: OTHER
First posted: 2018-03-19
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: NC vs noNC
Primary purpose: TREATMENT

Brief summary: The effects of a nutraceutical combination (NC) containing low-dose monacolin K and berberine on lipid profile, proprotein convertase subtilisin/kexin type 9 (PCSK9), subclinical inflammation and arterial stiffness were investigated in human immunodeficiency virus (HIV)-infected patients receiving stable antiretroviral therapy (ART).

Detailed description: This is a crossover interventional study of 26 HIV-infected patients on stable ART with low density lipoprotein cholesterol (LDL-C) \>100 mg/dL, not receiving any lipid-lowering treatment. After a 3-week lipid stabilization period with a standardized diet regimen, the effect of a 3-month oral NC containing red yeast rice-derived monacolin K 3 mg, berberine 500 mg, policosanol 10 mg, astaxanthin 0.5 mg, folic acid 0.2 mg and coenzyme Q10 2 mg vs no active treatment (noNC) was tested on plasma total cholesterol (TC), LDL-C, high density lipoprotein cholesterol (HDL-C), triglyceride, lipoprotein(a), PCSK9, high-sensitivity C-reactive protein (hsCRP) levels and aortic pulse wave velocity (aPWV).

Eligibility criteria: Inclusion Criteria:

* LDL-C \>100 mg/dL
* no history of cardiovascular disease
* stable ART for at least 6 months

Exclusion Criteria:

* current or recent (≤6 months) treatment with lipid-lowering drugs
* chronic kidney disease \[estimated glomerular filtration rate (GFR) \<60 ml/min\]
* liver impairment (AST and/or ALT \>3 times upper limit of normal)
* current pregnancy
* opportunistic infections within the past 3 months,
* having received an organ transplant/immunosuppressive therapy

Primary outcomes:
measure: Change from baseline in LDL-C levels at 3 months
timeFrame: 3 months after treatment randomization
Secondary outcomes:
measure: Change from baseline in PCSK9 levels at 3 months
timeFrame: 3 months after treatment randomization
measure: Change from baseline in subclinical inflammation at 3 months
timeFrame: 3 months after treatment randomization
measure: Change from baseline in arterial stiffness at 3 months
timeFrame: 3 months after treatment randomization
Other outcomes:
measure: Change from baseline in creatine phosphokinase (CPK) levels at 3 months
timeFrame: 3 months after treatment randomization
measure: Change from baseline in aspartate transaminase (AST) levels at 3 months
timeFrame: 3 months after treatment randomization
measure: Change from baseline in alanine transaminase (ALT) levels at 3 months
timeFrame: 3 months after treatment randomization
measure: Change from baseline in CD4+ cell count at 3 months
timeFrame: 3 months after treatment randomization
measure: Change from baseline in HIV-1 RNA levels at 3 months
timeFrame: 3 months after treatment randomization
Locations:
Study officials:
affiliation: University Of Perugia
name: Matteo Pirro, M.D., PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kelesidis T, Currier JS. Dyslipidemia and cardiovascular risk in human immunodeficiency virus infection. Endocrinol Metab Clin North Am. 2014 Sep;43(3):665-84. doi: 10.1016/j.ecl.2014.06.003.
citation: Chastain DB, Stover KR, Riche DM. Evidence-based review of statin use in patients with HIV on antiretroviral therapy. J Clin Transl Endocrinol. 2017 Feb 22;8:6-14. doi: 10.1016/j.jcte.2017.01.004. eCollection 2017 Jun.
citation: Bednasz C, Luque AE, Zingman BS, Fischl MA, Gripshover BM, Venuto CS, Gu J, Feng Z, DiFrancesco R, Morse GD, Ma Q. Lipid-Lowering Therapy in HIV-Infected Patients: Relationship with Antiretroviral Agents and Impact of Substance-Related Disorders. Curr Vasc Pharmacol. 2016;14(3):280-7. doi: 10.2174/1570161114666160106151652.
citation: Pirro M, Vetrani C, Bianchi C, Mannarino MR, Bernini F, Rivellese AA. Joint position statement on "Nutraceuticals for the treatment of hypercholesterolemia" of the Italian Society of Diabetology (SID) and of the Italian Society for the Study of Arteriosclerosis (SISA). Nutr Metab Cardiovasc Dis. 2017 Jan;27(1):2-17. doi: 10.1016/j.numecd.2016.11.122. Epub 2016 Nov 22.
citation: Pirro M, Mannarino MR, Ministrini S, Fallarino F, Lupattelli G, Bianconi V, Bagaglia F, Mannarino E. Effects of a nutraceutical combination on lipids, inflammation and endothelial integrity in patients with subclinical inflammation: a randomized clinical trial. Sci Rep. 2016 Mar 23;6:23587. doi: 10.1038/srep23587.
citation: Barrios V, Escobar C, Cicero AF, Burke D, Fasching P, Banach M, Bruckert E. A nutraceutical approach (Armolipid Plus) to reduce total and LDL cholesterol in individuals with mild to moderate dyslipidemia: Review of the clinical evidence. Atheroscler Suppl. 2017 Feb;24:1-15. doi: 10.1016/j.atherosclerosissup.2016.10.003. Epub 2016 Dec 18.
citation: Pirro M, Mannarino MR, Bianconi V, Simental-Mendia LE, Bagaglia F, Mannarino E, Sahebkar A. The effects of a nutraceutical combination on plasma lipids and glucose: A systematic review and meta-analysis of randomized controlled trials. Pharmacol Res. 2016 Aug;110:76-88. doi: 10.1016/j.phrs.2016.04.021. Epub 2016 May 6.
citation: Keithley JK, Swanson B, Sha BE, Zeller JM, Kessler HA, Smith KY. A pilot study of the safety and efficacy of cholestin in treating HIV-related dyslipidemia. Nutrition. 2002 Feb;18(2):201-4. doi: 10.1016/s0899-9007(01)00688-8.
citation: Kinlay S. Low-density lipoprotein-dependent and -independent effects of cholesterol-lowering therapies on C-reactive protein: a meta-analysis. J Am Coll Cardiol. 2007 May 22;49(20):2003-9. doi: 10.1016/j.jacc.2007.01.083. Epub 2007 May 4.
citation: Pirro M, Francisci D, Bianconi V, Schiaroli E, Mannarino MR, Barsotti F, Spinozzi A, Bagaglia F, Sahebkar A, Baldelli F. NUtraceutical TReatment for hYpercholesterolemia in HIV-infected patients: The NU-TRY(HIV) randomized cross-over trial. Atherosclerosis. 2019 Jan;280:51-57. doi: 10.1016/j.atherosclerosis.2018.11.026. Epub 2018 Nov 14.