Role of PPAR-y Agonists in Immunomodulation and Vascular Prevention in SLE (PPAR-SLE)
Condition: Systemic Lupus Erythematosus
MeSH terms: Lupus Erythematosus, Systemic
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      Background:

      - Lupus causes a person s immune system to attack the body. It can cause blood vessel
      problems, heart attack, or stroke. Researchers want to see if the drug pioglitazone may help.

      Objectives:

      - To see how well pioglitazone improves blood vessel function and decreases blood vessel
      inflammation. To study its effect on lupus symptoms.

      Eligibility:

      - Adults at least 18 years old with lupus.

      Design:

        -  Participants will be screened with medical history, heart test, and blood and urine
           tests. They may have a bone density test.

        -  Visit 1:

        -  Participants will have:

        -  Physical exam and blood drawn.

        -  Peripheral Arterial Tonometry (Endopat). A cup will be placed on the finger and a
           pressure cuff on the arm.

        -  Cardio-ankle vascular index (CAVI) and/or Sphygmocor. Electrodes will be placed on both
           wrists, a microphone on the chest, and a blood pressure cuff on each arm and leg.
           Another test will involve placing a small device on a fingertip.

        -  18-Fluorodeoxyglucose (FDG) positron emission tomography/computerized tomography
           (PET/CT) (some participants). A radioactive sugar will be injected into a small plastic
           tube in an arm vein. Participants will lie on a bed that moves in and out of a scanner
           that takes pictures.

        -  Participants will get a 3-month-supply of the study drug or placebo. After 1 week, their
           dose may increase.

        -  After those 3 months, they will not take either drug for 8 weeks. Then they will switch
           and take the other drug for 3 months.

        -  Participants will have 6 more visits over 8 months after Visit 1. Tests from Visit 1 may
           be repeated. They may have a urine test.
    

Detailed description: 
      Systemic lupus erythematosus (SLE) is an autoimmune disease of unclear cause that affects
      primarily women of childbearing age. Patients with lupus have a significantly increased risk
      of developing complications of their blood vessels due to accelerated hardening of the
      arteries (atherosclerosis). These complications include heart attacks and stroke. No drug to
      date has proven to prevent this type of complication in lupus and premature vascular disease
      significantly impacts the quality of life of these patients and enhances their risk of death.

      The thiazolidinediones (TZD) are a class of drugs approved for the treatment of patients with
      type 2 diabetes mellitus (DM); they belong to the family of drugs that activate the
      peroxisome proliferator-activated receptor-gamma (PPAR-gamma). They have been proposed to
      have strong anti-atherogenic and anti-inflammatory effects even in patients without diabetes.
      Recent work from our group and others indicates that TZDs significantly improve vascular
      damage, dysfunction of blood vessels and disease activity in mouse models of lupus and
      abrogate atherosclerosis. We recently identified the TZD pioglitazone as an effective drug in
      modulation of vascular function and disease activity in patients with rheumatoid arthritis.
      In addition, we have found in mouse models of lupus and in in vitro experiments with human
      lupus cells, that pioglitazone has important roles in modulating immune function and vascular
      manifestations. Furthermore, this drug is not immunosuppressive, adding an additional
      advantage when compared to other medications used in this disease.

      We propose that TZDs could significantly improve blood vessel function and play a role in
      atherosclerosis prevention in human SLE, in addition to modifying lupus disease activity. The
      major goal of the proposed research is to assess the effects of the PPAR-gamma agonist
      pioglitazone in SLE on vascular function and inflammation and on SLE disease activity. The
      results of the study may lead to the characterization of a new therapeutic target with dual
      effects on lupus and its associated blood vessel damage
    

Intervention name(s): PET/CT; Pioglitazone; Placebo
Intervention type(s): Radiation; Drug; Drug
Intervention description(s): The combined PET/CT scans provide images that pinpoint the anatomic location of abnormal metabolic activity within the body.; Increases insulin sensitivity in muscle and adipose tissue, and inhibits hepatic gluconeogenesis.
Intervention MeSH terms: Pioglitazone
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: Autoimmunity Pathogenesis; Atherosclerosis; Adult