Ignite Creation Date:
2024-05-06 @ 11:03 AM
Last Modification Date:
2024-10-26 @ 12:39 PM
Study NCT ID:
NCT03425630
Status:
COMPLETED
Last Update Posted:
2018-02-12
First Post:
2018-01-24
Brief Title:
LDL-cholesterol Lowering Effect of a New Dietary Supplement
Sponsor:
Ispharm srl
Organization:
Ispharm srl
Study Overview
Official Title:
LDL-cholesterol Lowering Effect of a New Dietary Supplement An Open-label Controlled Randomized Cross-over Clinical Trial in Patients With Mild-to-moderate Hypercholesterolemia
Status:
COMPLETED
Status Verified Date:
2018-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The aim of this study was to assess the lipid-lowering activity and safety of a dietary supplement containing monacolin K L-arginine coenzyme Q10 and ascorbic acid vitamin C
Twenty both gender caucasian outpatients aged 18-75 yrs with serum LDL-C between130-180 mgdL not significantly modified by an appropriate dietetic regimen assumed two different dietary supplements Argicolina trade mark A Normolip 5 trade mark N both containing monacolin K 10 mg for 8 weeks each separated by a 4-week wash-out period in a single center controlled randomized open-label cross-over clinical study Exclusion criteria were pregnancy or breast-feeding known liver renal or muscle diseases serum triglycerides TG greater than 350 mgdL previous cardiovascular events concomitant neoplastic or immunodepressive disease use of lipid-lowering drugs or dietary supplements within the last three weeks concurrent use of thiazide diuretics oral contraceptives containing estrogen or progestogen systemic corticosteroids use of psycho-active substances drug or alcohol abuse neurological or psychiatric diseases that could affect consent validity or impair the patients adherence to the study protocol Evaluation criteria were Tot-C LDL-C HDL-cholesterol TG fasting blood glucose aspartate aminotransferase alanine aminotransferase creatinkinase gamma-glutamyl-transpeptidase humeral blood pressure and heart rate measured at the start and a the end of each treatment period Safety was monitored through the study
Twenty both gender caucasian outpatients aged 18-75 yrs with serum LDL-C between130-180 mgdL not significantly modified by an appropriate dietetic regimen assumed two different dietary supplements Argicolina trade mark A Normolip 5 trade mark N both containing monacolin K 10 mg for 8 weeks each separated by a 4-week wash-out period in a single center controlled randomized open-label cross-over clinical study Exclusion criteria were pregnancy or breast-feeding known liver renal or muscle diseases serum triglycerides TG greater than 350 mgdL previous cardiovascular events concomitant neoplastic or immunodepressive disease use of lipid-lowering drugs or dietary supplements within the last three weeks concurrent use of thiazide diuretics oral contraceptives containing estrogen or progestogen systemic corticosteroids use of psycho-active substances drug or alcohol abuse neurological or psychiatric diseases that could affect consent validity or impair the patients adherence to the study protocol Evaluation criteria were Tot-C LDL-C HDL-cholesterol TG fasting blood glucose aspartate aminotransferase alanine aminotransferase creatinkinase gamma-glutamyl-transpeptidase humeral blood pressure and heart rate measured at the start and a the end of each treatment period Safety was monitored through the study
Detailed Description:
Between July 2016 and April 2017 eligible patients were recruited among the outpatients attending the Obesity Center of the Endocrinology Unit 1 Cisanello Hospital Pisa Italy Patients aged 18-75 years with serum LDL-C between130-180 mgdL not significantly modified by an appropriate dietetic regimen were considered eligible for the study Thirty patients all Caucasian were screened Ten were excluded during the screening process because they did not fulfill all the inclusion criteria screening failure Twenty patients were thus randomized 10 to the AN sequence and 10 to the NA sequence
Study design The study was conducted in a single center according to a controlled randomized open-label cross-over design Each patient had to assume in a randomized sequence both treatments A 1 sachetday N 1 capsuleday for 8 weeks each separated by a 4-week wash-out period The study plan included the initial screening visit V1 an entry visit at start of the first treatment period V2 a visit at the end of the first treatment period V3 56 5 days after V2 a wash-out period of 4 weeks 5 days a visit at start of the second crossed over treatment period V4 and a visit at the end of the second treatment period V5 56 5 days after V4 Figure 1 Tot-C LDL-C HDL-cholesterol HDL-C TG fasting blood glucose aspartate aminotransferase AST alanine aminotransferase ALT creatinkinase CK gamma-glutamyl-transpeptidase GGT humeral blood pressure and heart rate were measured at V1 V3 V4 and V5 Blood analyses were centrally performed in the laboratory of the Endocrinology Unit using standard enzymatic techniques LDL-C was measured directly Clinical safety was monitored throughout the study If required the patient could be re-evaluated at any time during the study aside of the visits scheduled
Statistical Methods The minimum level of statistical significance was set to p005 two-sided therefore 95 confidence limits 95CIs were calculated All reported p-values and CIs are two-sided
The primary efficacy variable was the LDL-C change between the start and the end of each treatment period expressed as a percentage of the initial value Therefore mean and 95CIs of changes within treatment periods from V2 to V3 and from V4 to V5 for the experimental and the control treatment irrespective of sequence were calculated The main analysis was the determination of the two-sided 95CI of the between-treatment mean difference in the primary variable Setting 010 ie 10 of the initial value as the minimum clinically relevant difference the two treatments were considered equivalent if the two-sided 95CI of the difference in their LDL-C change from baseline was entirely between -010 and 010 Parallel calculations were carried out on absolute rather than relative to baseline LDL-C changes Tot-C and HDL-C were analysed as described above for LDL-C for TG levels which were approximately log-normally distributed analogous calculations were performed on logarithmic transformations and changes were expressed as ratios Between-treatment comparisons were expressed as A-N differences for cholesterol values and as AN ratios for TG values The effects on LDL-C were additionally tested in sensitivity multivariate analyses split-plot analysis of variance for cross-over studies on final-baseline changes and analysis of covariance on the difference between the final values adjusted for sequence and for the difference between the baseline values Efficacy analyses had to be performed in the intention-to-treat population ie all patients with at least one post-baseline control A sensitivity analysis of the primary variable was also planned in the per-protocol population ie all patients without major protocol violations Safety results had to be reported in all patients who had assumed at least one dose of one study drug Statistical analyses were performed by the Studio Associato Airoldi Cicogna and Ghirri Milan using the SAS Software version 94 SAS Inc Cary NC
Sample Size The sample size was calculated for the main efficacy analysis described above ie the determination of the two-sided 95 CI of the between-treatment mean difference in the LDL-C change from baseline Assuming a standard deviation SD of the difference no greater than 012 based on a previous cross-over study for the difference between monacolin K and placebo 11 it was estimated that 18 patients were required to prove the equivalence with a power of 080 This figure was rounded to 20 enrolled patients allowing for possible exclusions from the analysis
Study design The study was conducted in a single center according to a controlled randomized open-label cross-over design Each patient had to assume in a randomized sequence both treatments A 1 sachetday N 1 capsuleday for 8 weeks each separated by a 4-week wash-out period The study plan included the initial screening visit V1 an entry visit at start of the first treatment period V2 a visit at the end of the first treatment period V3 56 5 days after V2 a wash-out period of 4 weeks 5 days a visit at start of the second crossed over treatment period V4 and a visit at the end of the second treatment period V5 56 5 days after V4 Figure 1 Tot-C LDL-C HDL-cholesterol HDL-C TG fasting blood glucose aspartate aminotransferase AST alanine aminotransferase ALT creatinkinase CK gamma-glutamyl-transpeptidase GGT humeral blood pressure and heart rate were measured at V1 V3 V4 and V5 Blood analyses were centrally performed in the laboratory of the Endocrinology Unit using standard enzymatic techniques LDL-C was measured directly Clinical safety was monitored throughout the study If required the patient could be re-evaluated at any time during the study aside of the visits scheduled
Statistical Methods The minimum level of statistical significance was set to p005 two-sided therefore 95 confidence limits 95CIs were calculated All reported p-values and CIs are two-sided
The primary efficacy variable was the LDL-C change between the start and the end of each treatment period expressed as a percentage of the initial value Therefore mean and 95CIs of changes within treatment periods from V2 to V3 and from V4 to V5 for the experimental and the control treatment irrespective of sequence were calculated The main analysis was the determination of the two-sided 95CI of the between-treatment mean difference in the primary variable Setting 010 ie 10 of the initial value as the minimum clinically relevant difference the two treatments were considered equivalent if the two-sided 95CI of the difference in their LDL-C change from baseline was entirely between -010 and 010 Parallel calculations were carried out on absolute rather than relative to baseline LDL-C changes Tot-C and HDL-C were analysed as described above for LDL-C for TG levels which were approximately log-normally distributed analogous calculations were performed on logarithmic transformations and changes were expressed as ratios Between-treatment comparisons were expressed as A-N differences for cholesterol values and as AN ratios for TG values The effects on LDL-C were additionally tested in sensitivity multivariate analyses split-plot analysis of variance for cross-over studies on final-baseline changes and analysis of covariance on the difference between the final values adjusted for sequence and for the difference between the baseline values Efficacy analyses had to be performed in the intention-to-treat population ie all patients with at least one post-baseline control A sensitivity analysis of the primary variable was also planned in the per-protocol population ie all patients without major protocol violations Safety results had to be reported in all patients who had assumed at least one dose of one study drug Statistical analyses were performed by the Studio Associato Airoldi Cicogna and Ghirri Milan using the SAS Software version 94 SAS Inc Cary NC
Sample Size The sample size was calculated for the main efficacy analysis described above ie the determination of the two-sided 95 CI of the between-treatment mean difference in the LDL-C change from baseline Assuming a standard deviation SD of the difference no greater than 012 based on a previous cross-over study for the difference between monacolin K and placebo 11 it was estimated that 18 patients were required to prove the equivalence with a power of 080 This figure was rounded to 20 enrolled patients allowing for possible exclusions from the analysis
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None