Extended Release Niacin and Fenofibrate for the Treatment of Atherogenic Dyslipidemia in Obese Females
Condition: Atherogenic Dyslipidemia; Obesity Associated Disorder
MeSH terms: Dyslipidemias
Study type: Interventional
Phase: Phase 4

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.
    

Intervention name(s): Therapeutic Lifestyle Changes; Placebo; Fenofibrate; Wax Matrix Extended Release Niacin (WMER Niacin)
Intervention type(s): Other; Other; Drug; Dietary Supplement
Intervention description(s): Four-week therapeutic lifestyle changes run-in period, comprising individualized moderate physical activity and total calories reduction.
Other intervention name(s): Lipanthyl; ENDUR-ACIN®
Intervention MeSH terms: Niacin; Fenofibrate
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: Extended Release Niacin; Fenofibrate; treatment; Obesity; Atherogenic Dyslipidemia