Hypercholesterolemia
Conditions
Keywords
Lipids, Cholesterol, Triglycerides, Dyslipidemia, Low density lipoprotein cholesterol, Dietary Fats, Hyperlipidemias, Dietary Supplements, Food Supplements, Nutraceuticals, Nutriceuticals
Brief summary
High cholesterol is one of the major controllable risk factor for coronary heart disease. It is well demonstrated that drugs that reduce the intestinal absorption of cholesterol or block the synthesis of cholesterol or the association of both, can reduce cholesterol and reduce rate of cardiovascular events. The trial will evaluate natural alternative to this drug approach testing the effects of a combination of phytosterol, a nutritional that reduce cholesterol absorption, and fermented red rice, a nutritional that reduce the synthesis of cholesterol. Subjects with sub optimal blood cholesterol levels, matching all the inclusion criteria and none of the exclusion criteria, will be treated for 8 weeks with a nutraceutical combination of phytosterols and fermented red rice and will have to maintain, during the entire duration of the study, the Mediterranean-style diet provided. The study will evaluate as primary objective the changes in LDL cholesterol blood levels and more in general the modulation of lipid profile and of others clinical parameters as well as the tolerability.
Detailed description
The study is made up of four visits distributed over a 10-weeks period: V 1 (day -14) - Screening: After providing written informed consent, tests will be run in order to check the subject's eligibility for the study. Subjects will also be given suggestions regarding their diet (a Mediterranean-style diet is to be maintained for the entire duration of the study). V2 (baseline) and Day 0 (randomization): After confirmation of the subject's eligibility \[LDL-C and Triglycerides (TG) criteria confirmed with blood test results\], eligible subjects will be randomized within 3 days to one of the two treatment groups. During this visit an endothelial reactivity test will be performed. V3 (28 ±3 days after Day 0) - Intermediate: Blood will be drawn for tests and compliance with treatment will be assessed. V4 (28 ± 3 days after Visit 3) - End of study: Blood tests and an endothelial reactivity test will be performed and treatment compliance will be assessed. Weight, waist circumference, Index of Central Obesity (ICO) and Body Mass Index (BMI), Hepatic Steatosis Index (HSI) and Lipid Accumulation Product (LAP) will be measured/calculated at each visit, height at Visit 1. Heart rate and blood pressure will be measured at each visit. Adverse events (AEs) will be collected throughout the study starting from the Informed consent signature. The study will be monitored according to the details specified in the Monitoring Plan. The monitor will have the responsibility of reviewing the ongoing study with the Investigator to verify adherence to the protocol and to deal with any problems. Case Report Form (CRF) will be checked for completeness and consistency with the source data and special attention will be dedicated to patient enrolment, obtaining signed informed consent, occurrence of AEs, product accountability, and accurate recording of variables. The confidentiality of study related documents shall be maintained at all times. The Investigator agrees to allow access to all study materials needed for the proper review of study conduct. An independent quality audit/inspection at the study site may take place at any time during or after the study. The independent audit/inspection can be carried out by the Sponsor's independent Quality Assurance (QA), by a Health Authorities or an Ethics Committee (EC).
Interventions
DIETARY_SUPPLEMENTNutraceutical combination
One tablet per os per day to be taken in the evening from randomization (day 0) to the end of the trial (day 56 +/- 3)
OTHERPlacebo
One tablet per os per day to be taken in the evening from randomization (day 0) to the end of the trial (day 56 +/- 3)
Sponsors
A. Menarini Industrie Farmaceutiche Riunite S.r.l.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
30 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
\- Subjects must meet all of the following inclusion criteria: * Age 30-75 years * LDL-cholesterol = 115 -190 mg/dL * Triglycerides \< 400 mg/dL * Any cardiovascular therapy should be stable for type and dose for at least three months * Signed, written informed consent
Exclusion criteria
\- Subjects must meet none of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Blood LDL Cholesterol Level | From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment | Mean change in blood LDL cholesterol level from randomization (day 0) to V4 (week 8) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Blood HDL Cholesterol Level | From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment | Mean change in blood HDL cholesterol level from randomization (day 0) to V4 (week 8) |
| Change in Blood Non-HDL Cholesterol Level | From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment | Mean change in blood non-HDL cholesterol level from randomization (day 0) to V4 (week 8) |
| Change in Blood Triglycerides Level | From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment | Mean change in blood triglycerides level from randomization (day 0) to V4 (week 8) |
| Change in Blood Apolipoprotein B Level | From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment | Mean change in blood apolipoprotein B level from randomization (day 0) to V4 (week 8) |
| Change in Total Cholesterol/HDL Cholesterol Ratio | From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment | Mean change in total cholesterol/HDL cholesterol ratio from randomization (day 0) to V4 (week 8) |
| Change in Total LDL Cholesterol/HDL Cholesterol Ratio | From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment | Mean change in LDL/HDL cholesterol ratio from randomization (day 0) to V4 (week 8) |
| Change in Pulse Volume (PV) Waveform (Endothelial Reactivity) | From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment | Mean change in Pulse Volume (PV) waveform from randomization (day 0) to V4 (week 8). PV unit of measurement is a percent change in the PV waveform area, comparing waveforms during and before hyperemia through the equation √PV2/PV1 that relates PV at baseline (PV1) and PV during hyperemia (PV2). |
| Change in Total Blood Cholesterol Level | From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment | Mean change in total blood LDL cholesterol level from randomization (day 0) to V4 (week 8) |
| Change in Aspartate Aminotransferase (AST) | From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment | Mean change in aspartate aminotransferase from randomization (day 0) to V4 (week 8) |
| Change in Alanine Aminotransferase (ALT) | From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment | Mean change in aspartate aminotransferase from randomization (day 0) to V4 (week 8) |
| Change in Gamma Glutamyl Transpeptidase (GGT) | From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment | Mean change gamma glutamyl transpeptidase (GGT) from randomization (day 0) to V4 (week 8) |
| Change in Serum Creatinine | From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment | Mean change in Serum Creatinine values from randomization (day 0) to V4 (week 8) |
| Change in Serum Uric Acid | From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment | Mean change in Serum uric acid values from randomization (day 0) to V4 (week 8) |
| Change in Creatine Phosphokinase (CPK) | From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment | Mean change in creatine phosphokinase (CPK) from randomization (day 0) to V4 (week 8) |
| Change in Glycemia | From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment | Mean change in Glycemia from randomization (day 0) to V4 (week 8) |
Countries
Italy
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Nutraceutical Combination One film-coated tablet (1300 mg) per os per day to be taken in the evening. Each tablet contains phytosterols 800 mg, Monascus purpureus (167 mg) titrated at 3% in monacolin K (5 mg), niacin 27 mg, linear aliphatic alcohols titrated to 60% octacosanol.
Nutraceutical combination: One tablet per os per day to be taken in the evening from randomization (day 0) to the end of the trial (day 56 +/- 3) | 43 |
| Placebo One film-coated tablet (1300 mg) per os per day to be taken in the evening. Placebo tablets identical in appearance, size, shape, weight and taste to the active product.
Placebo: One tablet per os per day to be taken in the evening from randomization (day 0) to the end of the trial (day 56 +/- 3) | 42 |
| Total | 85 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Nutraceutical Combination | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 51.28 years STANDARD_DEVIATION 9.56 | 51.79 years STANDARD_DEVIATION 10.74 | 51.53 years STANDARD_DEVIATION 10.1 |
| LDL blood cholesterol level | 154.27 mg/dL STANDARD_DEVIATION 20.47 | 160.57 mg/dL STANDARD_DEVIATION 20.84 | 157.38 mg/dL STANDARD_DEVIATION 20.77 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 43 Participants | 42 Participants | 85 Participants |
| Region of Enrollment Italy | 43 participants | 42 participants | 85 participants |
| Sex: Female, Male Female | 24 Participants | 23 Participants | 47 Participants |
| Sex: Female, Male Male | 19 Participants | 19 Participants | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 43 | 0 / 42 |
| other Total, other adverse events | 0 / 43 | 0 / 42 |
| serious Total, serious adverse events | 0 / 43 | 0 / 42 |
Outcome results
Primary
Change in Blood LDL Cholesterol Level
Mean change in blood LDL cholesterol level from randomization (day 0) to V4 (week 8)
Time frame: From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment
Population: Population analysed is the Full Analysis Set one (FAS), composed by all randomization subjects who completed all the visits and were assessed for LDL cholesterol at last visit (Visit 4 - Week 8).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nutraceutical Combination | Change in Blood LDL Cholesterol Level | -32.48 mg/dL | Standard Deviation 30.18 |
| Placebo | Change in Blood LDL Cholesterol Level | 2.54 mg/dL | Standard Deviation 19.44 |
p-value: <0.000195% CI: [-48.57, -29.75]ANCOVA
Secondary
Change in Alanine Aminotransferase (ALT)
Mean change in aspartate aminotransferase from randomization (day 0) to V4 (week 8)
Time frame: From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment
Population: Population analysed is the Full Analysis Set one (FAS), composed by all randomization subjects who completed all the visits and were assessed for LDL cholesterol at last visit (Visit 4 - Week 8).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nutraceutical Combination | Change in Alanine Aminotransferase (ALT) | 4.53 U/L | Standard Deviation 9.29 |
| Placebo | Change in Alanine Aminotransferase (ALT) | 2.93 U/L | Standard Deviation 9.75 |
p-value: 0.265495% CI: [-4.66, 16.69]ANCOVA
Secondary
Change in Aspartate Aminotransferase (AST)
Mean change in aspartate aminotransferase from randomization (day 0) to V4 (week 8)
Time frame: From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment
Population: Population analysed is the Full Analysis Set one (FAS), composed by all randomization subjects who completed all the visits and were assessed for LDL cholesterol at last visit (Visit 4 - Week 8).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nutraceutical Combination | Change in Aspartate Aminotransferase (AST) | 0.98 U/L | Standard Deviation 4.01 |
| Placebo | Change in Aspartate Aminotransferase (AST) | 0.86 U/L | Standard Deviation 3.4 |
p-value: 0.926695% CI: [-1.63, 1.48]ANCOVA
Secondary
Change in Blood Apolipoprotein B Level
Mean change in blood apolipoprotein B level from randomization (day 0) to V4 (week 8)
Time frame: From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment
Population: Population analysed is the Full Analysis Set one (FAS), composed by all randomization subjects who completed all the visits and were assessed for LDL cholesterol at last visit (Visit 4 - Week 8).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nutraceutical Combination | Change in Blood Apolipoprotein B Level | -14.79 mg/dL | Standard Deviation 15.05 |
| Placebo | Change in Blood Apolipoprotein B Level | 1.6 mg/dL | Standard Deviation 14.29 |
p-value: <0.000195% CI: [-23.54, -10.98]ANCOVA
Secondary
Change in Blood HDL Cholesterol Level
Mean change in blood HDL cholesterol level from randomization (day 0) to V4 (week 8)
Time frame: From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment
Population: Population analysed is the Full Analysis Set one (FAS), composed by all randomization subjects who completed all the visits and were assessed for LDL cholesterol at last visit (Visit 4 - Week 8).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nutraceutical Combination | Change in Blood HDL Cholesterol Level | 0.78 mg/dL | Standard Deviation 7.17 |
| Placebo | Change in Blood HDL Cholesterol Level | 1.11 mg/dL | Standard Deviation 7.37 |
p-value: 0.95195% CI: [-2.87, 3.05]ANCOVA
Secondary
Change in Blood Non-HDL Cholesterol Level
Mean change in blood non-HDL cholesterol level from randomization (day 0) to V4 (week 8)
Time frame: From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment
Population: Population analysed is the Full Analysis Set one (FAS), composed by all randomization subjects who completed all the visits and were assessed for LDL cholesterol at last visit (Visit 4 - Week 8).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nutraceutical Combination | Change in Blood Non-HDL Cholesterol Level | -33.35 mg/dL | Standard Deviation 22.99 |
| Placebo | Change in Blood Non-HDL Cholesterol Level | 3.65 mg/dL | Standard Deviation 18.78 |
p-value: <0.000195% CI: [-51.58, -31.82]ANCOVA
Secondary
Change in Blood Triglycerides Level
Mean change in blood triglycerides level from randomization (day 0) to V4 (week 8)
Time frame: From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment
Population: Population analysed is the Full Analysis Set one (FAS), composed by all randomization subjects who completed all the visits and were assessed for LDL cholesterol at last visit (Visit 4 - Week 8).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nutraceutical Combination | Change in Blood Triglycerides Level | -1.44 mg/dL | Standard Deviation 42.76 |
| Placebo | Change in Blood Triglycerides Level | 17.62 mg/dL | Standard Deviation 60.48 |
p-value: 0.192495% CI: [-17.59, 3.59]ANCOVA
Secondary
Change in Creatine Phosphokinase (CPK)
Mean change in creatine phosphokinase (CPK) from randomization (day 0) to V4 (week 8)
Time frame: From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment
Population: Population analysed is the Full Analysis Set one (FAS), composed by all randomization subjects who completed all the visits and were assessed for LDL cholesterol at last visit (Visit 4 - Week 8).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nutraceutical Combination | Change in Creatine Phosphokinase (CPK) | 2.09 U/L | Standard Deviation 48.76 |
| Placebo | Change in Creatine Phosphokinase (CPK) | -7.00 U/L | Standard Deviation 56.56 |
p-value: 0.722495% CI: [-7.83, 11.25]ANCOVA
Secondary
Change in Gamma Glutamyl Transpeptidase (GGT)
Mean change gamma glutamyl transpeptidase (GGT) from randomization (day 0) to V4 (week 8)
Time frame: From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment
Population: Population analysed is the Full Analysis Set one (FAS), composed by all randomization subjects who completed all the visits and were assessed for LDL cholesterol at last visit (Visit 4 - Week 8).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nutraceutical Combination | Change in Gamma Glutamyl Transpeptidase (GGT) | 0.91 U/L | Standard Deviation 9.83 |
| Placebo | Change in Gamma Glutamyl Transpeptidase (GGT) | 3.07 U/L | Standard Deviation 9.53 |
p-value: 0.259595% CI: [-16.37, 4.47]ANCOVA
Secondary
Change in Glycemia
Mean change in Glycemia from randomization (day 0) to V4 (week 8)
Time frame: From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment
Population: Population analysed is the Full Analysis Set one (FAS), composed by all randomization subjects who completed all the visits and were assessed for LDL cholesterol at last visit (Visit 4 - Week 8).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nutraceutical Combination | Change in Glycemia | -0.88 mg/dL | Standard Deviation 6.26 |
| Placebo | Change in Glycemia | -1.57 mg/dL | Standard Deviation 5.78 |
p-value: 0.559495% CI: [-1.76, 3.24]ANCOVA
Secondary
Change in Pulse Volume (PV) Waveform (Endothelial Reactivity)
Mean change in Pulse Volume (PV) waveform from randomization (day 0) to V4 (week 8). PV unit of measurement is a percent change in the PV waveform area, comparing waveforms during and before hyperemia through the equation √PV2/PV1 that relates PV at baseline (PV1) and PV during hyperemia (PV2).
Time frame: From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment
Population: Population analysed is the Full Analysis Set one (FAS), composed by all randomization subjects who completed all the visits and were assessed for LDL cholesterol at last visit (Visit 4 - Week 8).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nutraceutical Combination | Change in Pulse Volume (PV) Waveform (Endothelial Reactivity) | -0.08 percentage of change | Standard Deviation 0.25 |
| Placebo | Change in Pulse Volume (PV) Waveform (Endothelial Reactivity) | -0.03 percentage of change | Standard Deviation 0.21 |
p-value: 0.453595% CI: [-12.64, 5.7]ANCOVA
Secondary
Change in Serum Creatinine
Mean change in Serum Creatinine values from randomization (day 0) to V4 (week 8)
Time frame: From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment
Population: Population analysed is the Full Analysis Set one (FAS), composed by all randomization subjects who completed all the visits and were assessed for LDL cholesterol at last visit (Visit 4 - Week 8).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nutraceutical Combination | Change in Serum Creatinine | 0 mg/dL | Standard Deviation 0.08 |
| Placebo | Change in Serum Creatinine | 0 mg/dL | Standard Deviation 0.1 |
p-value: 0.847695% CI: [-0.039, 0.032]ANCOVA
Secondary
Change in Serum Uric Acid
Mean change in Serum uric acid values from randomization (day 0) to V4 (week 8)
Time frame: From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment
Population: Population analysed is the Full Analysis Set one (FAS), composed by all randomization subjects who completed all the visits and were assessed for LDL cholesterol at last visit (Visit 4 - Week 8).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nutraceutical Combination | Change in Serum Uric Acid | -0.30 mg/dL | Standard Deviation 0.98 |
| Placebo | Change in Serum Uric Acid | 0 mg/dL | Standard Deviation 0.56 |
p-value: 0.149995% CI: [-0.49, 0.08]ANCOVA
Secondary
Change in Total Blood Cholesterol Level
Mean change in total blood LDL cholesterol level from randomization (day 0) to V4 (week 8)
Time frame: From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment
Population: Population analysed is the Full Analysis Set one (FAS), composed by all randomization subjects who completed all the visits and were assessed for LDL cholesterol at last visit (Visit 4 - Week 8).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nutraceutical Combination | Change in Total Blood Cholesterol Level | -31.99 mg/dL | Standard Deviation 34.05 |
| Placebo | Change in Total Blood Cholesterol Level | 7.17 mg/dL | Standard Deviation 21.1 |
p-value: 0.000195% CI: [-51.73, -30.74]ANCOVA
Secondary
Change in Total Cholesterol/HDL Cholesterol Ratio
Mean change in total cholesterol/HDL cholesterol ratio from randomization (day 0) to V4 (week 8)
Time frame: From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment
Population: Population analysed is the Full Analysis Set one (FAS), composed by all randomization subjects who completed all the visits and were assessed for LDL cholesterol at last visit (Visit 4 - Week 8).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nutraceutical Combination | Change in Total Cholesterol/HDL Cholesterol Ratio | -0.79 ratio | Standard Deviation 0.79 |
| Placebo | Change in Total Cholesterol/HDL Cholesterol Ratio | 0.06 ratio | Standard Deviation 0.64 |
p-value: <0.000195% CI: [-1.19, -0.62]ANCOVA
Secondary
Change in Total LDL Cholesterol/HDL Cholesterol Ratio
Mean change in LDL/HDL cholesterol ratio from randomization (day 0) to V4 (week 8)
Time frame: From randomization (day 0) to V4 (week 8) for a total of 56 +/- 3 days of treatment
Population: Population analysed is the Full Analysis Set one (FAS), composed by all randomization subjects who completed all the visits and were assessed for LDL cholesterol at last visit (Visit 4 - Week 8).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nutraceutical Combination | Change in Total LDL Cholesterol/HDL Cholesterol Ratio | -0.76 ratio | Standard Deviation 0.7 |
| Placebo | Change in Total LDL Cholesterol/HDL Cholesterol Ratio | -0.01 ratio | Standard Deviation 0.52 |
p-value: <0.000195% CI: [-1.05, -0.59]ANCOVA