Fenofibrate Treatment in SCI
Condition: Spinal Cord Injury; Dyslipidemia
MeSH terms: Spinal Cord Injuries; Dyslipidemias
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      Cardiovascular disease-related morbidity in persons with spinal cord injury (SCI) occurs
      earlier in life, at a greater prevalence than that of the general population, and is the
      primary cause of death after the first year of injury. During the chronic phase of SCI, a
      characteristic dyslipidemia emerges, which is characterized by low serum high density
      lipoprotein cholesterol (HDL-C) concentrations, with values often qualifying to be an
      independent risk factor for coronary artery disease, and elevations in serum triglycerides
      (TG). Serum low density lipoprotein cholesterol concentrations in those with SCI are usually
      similar to those of the general population. The current proposal in persons with SCI aims to
      determine the safety and efficacy of short-term fenofibrate treatment, an anti-lipid
      medication whose primary action lowers serum TG and raises serum HDL-C levels.
    

Detailed description: 
      Although considered a modifiable risk factor for coronary artery disease (CAD) in the general
      population, the magnitude of physical activity required to promote cardiorespiratory fitness
      and a clinically meaningful change in blood-derived biomarkers of CAD is not achievable in
      those with a severe physical disability, such as with immobilizing paralysis from spinal cord
      injury (SCI). During the chronic phase of SCI, a characteristic dyslipidemia emerges, with
      mean serum high density lipoprotein cholesterol (HDL-C) concentrations <40 mg/dl, a threshold
      level for HDL-C that is appreciated to be an independent risk factor for CAD, elevations in
      triglycerides (TG) to concentrations at, or near, target values for the general population
      that trigger clinical intervention, and low density lipoprotein cholesterol (LDL-C)
      concentrations that are within the normal range. It should not be a surprise that
      cardiovascular disease (CVD)-related morbidity in persons with SCI occurs earlier in life, at
      a greater prevalence than that of the general population, and is the primary cause of death
      after the first year of injury. Population-based epidemiological studies are unavailable for
      clinical guidance because of the relatively low incidence rates for SCI. Clinical target
      values used to initiate treatment in the general population may be inappropriate in those
      with SCI because of their unique pathophysiology. In the absence of significant physical
      activity and lifestyle modifications, it would seem that appropriate pharmaceutical options
      are needed to properly manage markers of CVD-related risk in persons with SCI. To date, there
      is limited empirical evidence to support the use of lipid-lowering treatments in persons with
      SCI.

      Fenofibrate is a fibric acid derivate that activates peroxisome proliferator-activated
      receptor and lipoprotein lipase, leading to enhanced elimination of TG from plasma. In
      clinical trials where fenofibrate was used as a monotherapy, serum TG concentrations fell
      41-53%, very low density lipoprotein (VLDL) fell 38-52%, LDL-C decreased 6-20%, and HDL-C
      improved by as much as 20%. In consideration for the nature of dyslipidemia in persons with
      SCI, fenofibrate appears to be an appropriate first-line agent for treatment in this cohort,
      especially because most of those with SCI have LDL values that are within the clinically
      acceptable range. In the general population, standard clinical practice for lipid-lowering
      treatment with fenofibrate monotherapy follows a known and clinically accepted timeline to
      monitor safety and to determine therapeutic efficacy. It is recommended that, if after 2
      months of continuous therapy there are no beneficial changes to the lipoprotein profile, that
      treatment be discontinued (i.e., non-responders). Similarly, several large clinical trials
      have demonstrated that the peak therapeutic effects of fenofibrate are observed after 12-16
      weeks of treatment (i.e., responders). The proposed study will test the efficacy of
      administering fenofibrate to persons with SCI, a severely immobilized cohort that does not
      have established clinical practice guidelines to treat dyslipidemia and appears to have
      unique considerations that may be hypothesized to call for a more disease-specific approach
      for care. If successful, the treatment will reduce clinical markers of CVD-related risk by
      modifying the concentration and number of particles that are known to contribute to incident
      cardiac events and mortality. It is anticipated that the insight gained from this
      investigation will provide clinicians with a proof-of-concept for instituting appropriate use
      of lipid lowering agents to treat the dyslipidemia that has been well described in persons
      with SCI.
    

Intervention name(s): Fenofibrate; No intervention
Intervention type(s): Drug; Other
Intervention description(s): Fenofibrate is a peroxisome proliferator-activated receptor alpha agonist that is demonstrated to reduce triglyceride concentrations in the blood.; A cohort of participants will be randomized to receive no study drug, but will engage in study encounters.
Intervention MeSH terms: Fenofibrate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: tetraplegia; paraplegia; hypertriglyceridemia; hyperlipidemia; peroxisome proliferator-activated receptor alpha