Clinical trial NCT01811082: Comparison of Coenzyme A and Pantethine Capsule for Safety and Efficacy On Patients With Hyperlipidemia
Official title: Randomized Head-to-Head Comparison of Coenzyme A Capsule and Pantethine Capsule for Safety and Efficacy On Patients With Hyperlipidemia: A Phase III, Multicenter, Double-blinded, Double Dummy Clinical Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hyperlipoproteinemia
Lead sponsor: Zhejiang University
Sponsor class: OTHER
First posted: 2013-03-14
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to compare the lipid lowering effects and clinical safety of a natural hypolipidemic compound, coenzyme A capsule with a marketed drug, Pantethine Capsule, in Chinese patients with moderate dyslipidemia.

Detailed description: Hyperlipidemia plays important roles in the development and progression of atherosclerosis. Modulating lipid levels has been shown to reduce the development of atherosclerosis and incidence of cardiovascular disease. The HMG-CoA reductase inhibitors (also known as statins) are the most effective agents available in the management of hyperlipidemia and prevention of major cardiovascular events. Although statin based therapy is commonplace in primary and secondary prevention, several economical, clinical and safety issues have been raised, so that there is ongoing research into new, safer and more effective agents to be used alone or in combination with existing cardiovascular drugs.

Coenzyme A (CoA) is a ubiquitous essential cofactor that plays a central role in the metabolism of carboxylic acids, including short- and long-chain fatty acids, as well as carbohydrate and protein. In the metabolic pathway of lipid, CoA participates in fatty acid β-oxidation, promoting triglyceride (TG) catabolism. Previous research revealed that insufficiency of CoA in vivo influenced fatty acid β-oxidation catabolism and impaired clearance of TG from plasma, which was supposed to be one plausible reason resulting in type Ⅱb and Ⅳ hyperlipoproteinemia. In addition, epidemiological studies showed the prevalence of serum lipids level increased with age, which may be related to the reduction of CoA synthesis in aging individuals. Moreover, studies on animals have given evidence to prove that supplement of CoA had normalizing activity on plasma lipids in dyslipidemia.

Pantethine is a versatile and very well tolerated hypolipidemic agent that can decrease serum triglycerides, LDL cholesterol, and apolipoprotein B, while increasing HDL cholesterol and apolipoprotein A-I. Pantethine is the disulfide of pantetheine which per se occurs naturally as a product of coenzyme A catabolism. Theoretically, antihyperlipidemia effect of CoA should be more directly and effectively than pantethine. Researches on rabbits and rats models prove that high dose CoA orally can relieve fasting hyperlipidemia and insulin resistance induced by high fat diet. So far there has not been sufficient clinical research data to support the efficacy of CoA in dyslipidemia patients. The present study compares the safety and effectiveness of oral CoA and Pantetheine.

Eligibility criteria: Inclusion Criteria:

* TG 2.3～6.5mmol/l meeting the China National Cholesterol Education Programme diagnostic criteria of hyperlipidemia;
* 18-75 years of age;
* women of childbearing potential not using pharmacological or mechanical contraception or with a negative pregnancy test.

Exclusion Criteria:

* TC \>7.0 mmol/l;
* Body Mass Index \> 30 kg/m2
* drug induced secondary hypercholesterolemia (such as dibenzothiazine, contraceptive agent or adrenal cortex hormone)
* pregnancy
* acute coronary syndrome, acute myocardial infarction or undergone a revascularization procedure within 6 months
* acute liver disease or hepatic dysfunction, as determined by levels of alanine aminotransferase (ALT) or aspartate aminotransferase levels (AST) more than 3-fold the upper normal limit
* nephrotic syndrome or serum creatinine (Cr) (≥179 µmol/L) and creatine phosphokinase (CK) more than 3-fold the upper normal limit
* primary hypothyroidism
* psychiatric patients and HIV-infected patients
* poorly controlled hypertension, as indicated by a Systolic Blood Pressure \>180 mmHg or Diastolic Blood Pressure \>110 mmHg
* Type I diabetes mellitus（DM）, poorly controlled Type II DM (BS\>11.0 mmol/L ) or Type II DM with LDL-C \>2.6 mmol/L.Patients using immunosuppressive drugs, prohibited medication or other lipid-lowing drugs were also excluded. Subjects were also ineligible for the study if they had any severe disease.

Primary outcomes:
measure: serum triglyceride level
timeFrame: 10 months
Secondary outcomes:
measure: serum total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol levels
timeFrame: 10 months
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: 1st Affiliated Hospital, College of Medicine, Zhejiang University
state: Zhejiang
Study officials:
affiliation: Zhejiang University
name: Junzhu Chen, MD
role: STUDY_CHAIR
References: