Clinical trial NCT02422927: Nutraceutical Combination in Patients With Low-grade Systemic Inflammation
Official title: Effect of a Nutraceutical Combination on Endothelial Injury and C-reactive Protein in Patients With Low-grade Systemic Inflammation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Atherosclerosis
Inflammation
Hypercholesterolemia
Keywords: C-Reactive Protein
Endothelial Microparticles
Endothelium
Nutraceutical
Cholesterol
Lead sponsor: University Of Perugia
Sponsor class: OTHER
First posted: 2015-04-22
Enrollment: 100
Sex: ALL
Minimum age (years): 25
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The investigators tested if a nutraceutical combination with red yeast rice, berberine and policosanol (NC) can significantly modify inflammation, lipid profile and markers of endothelial injury (endothelial microparticles) in subjects with elevated levels of high-sensitivity C-reactive protein (hsCRP).

Detailed description: Will be included in the study 100 subjects with suboptimal LDL cholesterol levels (LDL 100-160 mg / dL) and hsCRP levels\> 2 mg / L, divided into two groups of equal numbers, matched by by sex and age, randomized to receive a nutraceutical combination containing red yeast 200 mg, berberine 500 mg and policosanol 10 mg (NC) in combination with a low-cholesterol diet (\<200 mg / day) or a low-cholesterol diet only (Standard of Care - SOC).

All subjects at the time of inclusion in the study protocol will be prescribed the SOC for a period of 30 days (Lipid Stabilization Period: LSP); After 30 days LSP it will be performed randomization in the two intervention arms: NC + SOC or SOC.

Eligibility criteria: Inclusion Criteria:

* LDL cholesterol \<160 mg/dl (4,14 mmol/l);
* hsCRP \>2 mg/L;

Exclusion Criteria:

* triglycerides \>500 mg/dL (5.6 mmol/L);
* current or previous treatment with lipid-lowering drugs or with other drugs supposed to modify vascular damage and/or repair (antiplatelet, anti-hypertensive and antioxidant drugs);
* current or previous treatment with hormone replacement therapy for menopause vasomotor symptoms;
* evidence of liver dysfunction or alanine-aminotransferase (ALT) levels twice above the upper normal limit;
* creatin-kinase (CK) levels thrice above the upper normal limit
* history or clinical evidence of previous or current cardiovascular disease;
* presence of strong cardiovascular risk factors such as: serum creatinine levels \>2 mg/dL, diabetes mellitus, uncontrolled systemic arterial hypertension (systolic blood pressure \>190 mg/dL or diastolic blood pressure \>100 mg/dL); history of cancer in the former 5 years before recruitment; not adequately treated hypothyroidism (TSH levels \>1,5 times the upper normal limit);
* history of malignancy in the previous 5 years before screening;
* not adequately treated hypothyroidism (TSH levels \>1,5 times the upper normal limit);
* previous or current alcohol or drugs abuse;
* history or clinical evidence of chronic inflammatory disease such as severe arthritis, systemic lupus erythematosus or chronic inflammatory bowel disease;
* current or previous use of immunosuppressant agents or long term glucocorticoids
* history or clinical evidence of any severe concomitant disease which may compromise subject's safety or its possibility to carry out the study.

Primary outcomes:
measure: Change from Baseline in LDL cholesterol at 3 months
timeFrame: 3 months after treatment randomization
Secondary outcomes:
measure: Change from Baseline in Circulating endothelial microparticles at 3 months
timeFrame: 3 months after treatment randomization
measure: Change from Baseline in C-reactive protein at 3 months
timeFrame: 3 months after treatment randomization
Other outcomes:
Locations:
Study officials:
affiliation: University Of Perugia
name: Matteo Pirro, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: St-Pierre AC, Cantin B, Bergeron J, Pirro M, Dagenais GR, Despres JP, Lamarche B. Inflammatory markers and long-term risk of ischemic heart disease in men A 13-year follow-up of the Quebec Cardiovascular Study. Atherosclerosis. 2005 Oct;182(2):315-21. doi: 10.1016/j.atherosclerosis.2005.02.009.
citation: Ridker PM, Rifai N, Clearfield M, Downs JR, Weis SE, Miles JS, Gotto AM Jr; Air Force/Texas Coronary Atherosclerosis Prevention Study Investigators. Measurement of C-reactive protein for the targeting of statin therapy in the primary prevention of acute coronary events. N Engl J Med. 2001 Jun 28;344(26):1959-65. doi: 10.1056/NEJM200106283442601.
citation: Pirro M, Schillaci G, Paltriccia R, Bagaglia F, Menecali C, Mannarino MR, Capanni M, Velardi A, Mannarino E. Increased ratio of CD31+/CD42- microparticles to endothelial progenitors as a novel marker of atherosclerosis in hypercholesterolemia. Arterioscler Thromb Vasc Biol. 2006 Nov;26(11):2530-5. doi: 10.1161/01.ATV.0000243941.72375.15. Epub 2006 Aug 31.
citation: Pirro M, Schillaci G, Bagaglia F, Menecali C, Paltriccia R, Mannarino MR, Capanni M, Velardi A, Mannarino E. Microparticles derived from endothelial progenitor cells in patients at different cardiovascular risk. Atherosclerosis. 2008 Apr;197(2):757-67. doi: 10.1016/j.atherosclerosis.2007.07.012. Epub 2007 Aug 27.
citation: Affuso F, Ruvolo A, Micillo F, Sacca L, Fazio S. Effects of a nutraceutical combination (berberine, red yeast rice and policosanols) on lipid levels and endothelial function randomized, double-blind, placebo-controlled study. Nutr Metab Cardiovasc Dis. 2010 Nov;20(9):656-61. doi: 10.1016/j.numecd.2009.05.017. Epub 2009 Aug 20.