Clinical trial NCT03615534: Extended Release Niacin and Fenofibrate for the Treatment of Atherogenic Dyslipidemia in Obese Females
Official title: Efficacy and Safety of Extended Release Niacin-Fenofibrate Combination and Monotherapy for the Treatment of Atherogenic Dyslipidemia in Obese Females
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Atherogenic Dyslipidemia
Obesity Associated Disorder
Keywords: Extended Release Niacin
Fenofibrate
treatment
Obesity
Atherogenic Dyslipidemia
Lead sponsor: Al-Kindy College of Medicine
Sponsor class: OTHER
Collaborators: name: Al-Kindy College of Medicine
First posted: 2018-08-06
Enrollment: 161
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: Atherogenic Dyslipidemia (AD) is a risk-conferring lipid/lipoprotein profile that comprises a higher proportion of small LDL particles, reduced HDL-C, and increased triglycerides. It is characteristically seen in patients with obesity, metabolic syndrome, insulin resistance, and type 2 diabetes mellitus and has emerged as an important marker for the increased cardiovascular disease (CVD) risk observed in these populations.

Optimal cardiovascular risk reduction in patients exhibiting the lipid triad of AD requires integrated pharmacotherapy to normalize HDL-C, Triglyceride (TG) and LDL-C levels. Recent studies have focused on optimizing treatment for AD and compare the efficacy and tolerability of combined lipid-altering drug based therapies, however, an optimal pharmacologic approach has not yet been established.

The present study was intended to evaluate the restorative efficacy of Extended Release Niacin (ER Niacin) and Fenofibrate as mono and combination therapies , as well as their safety and tolerability in females with obesity-induced AD.

Detailed description: Study Setting:

The present study is a single blinded placebo-controlled randomized clinical trial, in which target individuals were obese females (BMI≥30 kg/m2), within the age of 20-60 years, attending the Obesity research and therapy unit of Al-Kindy College of Medicine, University of Baghdad (Baghdad, Iraq), throughout the period from 1st October 2014 to 15th March 2015.

Study Protocol:

Target individuals with fulfill devoid of exclusion criteria, were further screened and only candidates with conventional diagnosis of AD, as confirmed by a fasting serum TG \>150 mg/dl coincide with an HDL-C of less than 50 mg/dl, were considered to be enrolled. Finally, and successive to a comprehensible concise for the expected benefits and side effects on top of the commitment to the entire protocol, eligible candidates settled for participation were provided with a written informed consent.

Enrollment:

1. Therapeutic Lifestyle Changes (TLC) Run-in Period: Each and every eligible candidate was enrolled in a four-week TLC run-in (or lead-in) period to exclude responders and to obtain baseline data for non-responders prior to randomization.
2. Randomization and Treatment Allocation: TLC non-responders with persistent AD were randomly allocated to one of the four treatment arms. In order to ensure a periodical balance among all study groups in the course of treatment allocation, permuted-block randomization with a block size of four was implemented and the system produced by this approach was adopted for the sequential random assignment of patients to treatment arms. .

Discontinuation of Treatment:

Although the absence of published consensus on drug discontinuation in the face of laboratory abnormalities has permitted a spectrum of indefinite decisions, mainly driven by clinical experience, clinical status and tolerability of the patient. For the present study discontinuation of treatment is considered if:

1. Adverse events including flushing, nausea, vomiting, muscle pain, or dizziness turn sever enough to surpass patient's tolerability.
2. Estimated glomerular filtration rate (eGFR) is reduced to ˂ 60ml/min per 1.73 m2 indicating renal insufficiency.
3. Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) increased to\>3 Upper Limit of Normal (ULN) with the appearance of nausea, vomiting, fatigue, right upper quadrant pain or tenderness, fever, and/or rash.
4. Serum uric acid exceeds the critical value of 6mg/dl.

Assessment of Treatments Responses:

Responses to the different treatments arms, in terms of efficacy and safety, are assessed by analyzing clinical and laboratory data collected at each visit over the entire course of the study, including a thorough medical history and previous medication records.

Statistical Analysis:

All statistical analyses were executed via the statistical package SPSS version 17.0 (SPSS, Inc.). Prior to analysis, Shapiro-Wilk test was used for assessing the normality of distributions for continuous variables, with the data expressed as the mean ± standard error (SE). Analysis of variance (ANOVA) was applied to compare the means of baseline characteristics among different treatments groups. Comprising the influence of the baseline level as a covariate, analysis of covariance (ANCOVA), embracing the least significant difference (LSD) for pair-wise comparison, was applied to assess treatment effects and safety profiles among different arms. Results were evaluated in terms of adjusted end line levels and percent changes from baseline levels. Multivariate Analysis of Covariance (MANCOVA), on the other hand, with further adjustments for relevant covariates was conducted whenever needed. Probability of less than 0.05 was considered statistically significant.

Eligibility criteria: Inclusion Criteria:

* BMI≥30 kg/m2.
* Conventional diagnosis of atherogenic dyslipidemia, confirmed by a fasting serum TG more than150 mg/dl coincide with an HDL-C of less than 50 mg/dl.

Exclusion Criteria:

* The use of any antilipidemic medication.
* Findings suggestive for renal dysfunction (eGFR˂60ml/min per 1.73 m2).
* Findings suggestive for hepatic insufficiency (ALT and/or AST˃2ULN).
* Clinical or laboratory findings suggestive for thyroid dysfunction.
* Established diagnosis of Diabetes Mellitus.
* History of gout, hyperuricemia, or on hypouricemic agents.
* Active peptic ulcer.
* Pregnancy, or nursing mothers.
* Alcohol or tobacco consumption.

Primary outcomes:
measure: Changes Serum Triglyceride Levels
timeFrame: Treatments effects were assessed by two events, baseline investigations conducted before randomization and end line investigations at the end of the eighth week of treatments.
measure: Changes in Serum Lipoprotein Cholesterol Levels
timeFrame: Treatments effects were assessed by two events, baseline investigations conducted before randomization and end line investigations at the end of the eighth week of treatments.
measure: Changes in Serum Apolipoprotein Levels
timeFrame: Treatments effects were assessed by two events, baseline investigations conducted before randomization and end line investigations at the end of the eighth week of treatments.
Secondary outcomes:
measure: Changes in Serum Fasting Glucose Levels.
timeFrame: Changes from baseline were assessed at the end eighth week of treatments.
measure: Changes in Estimated Glomerular Filtration Rate (eGFR)
timeFrame: Changes from baseline were assessed at the end of the eighth week of treatments.
measure: Changes in Serum Uric Acid Levels
timeFrame: Changes from baseline were assessed at the end of the eighth week of treatments.
measure: Changes in Serum Enzymes Levels
timeFrame: Changes from baseline were assessed at the end of the eighth week of treatments.
measure: Changes in Systolic and Diastolic Blood Pressure
timeFrame: Changes from baseline were assessed at the end of the eighth week of treatments.
measure: Adverse Events
timeFrame: Changes from baseline were assessed at the end of the eighth week of treatments.
Other outcomes:
Locations:
city: Baghdad
country: Iraq
facility: Al Kindy College of Medicine, University of Baghdad
city: Baghdad
country: Iraq
facility: Lewai S Abdulaziz
Study officials:
affiliation: Al-Kindy college of Medicine, University of Baghdad
name: Lewai S Abdulaziz, MSc PhD
role: STUDY_CHAIR
affiliation: College of Pharmacy, University of Baghdad
name: May S Al-Sabbagh, MSc
role: STUDY_CHAIR
affiliation: College of Pharmacy, University of Baghdad
name: Marwah S Attar, MSc
role: STUDY_DIRECTOR
affiliation: Al-Kindy college of Medicine, University of Baghdad
name: Faris A Khazaal, FRCP
role: PRINCIPAL_INVESTIGATOR
References: