Efficacy of Amlexanox vs. Placebo in Type 2 Diabetic Patients
Condition: Diabetes Mellitus Type 2; Non-alcoholic Fatty Liver Disease; Obesity
MeSH terms: Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Amlexanox; Placebo
Intervention description: 25 mg amlexanox tablets blinded by encapsulation; placebo sham blinded by encapsulation in the same capsules as the study drug arm
Intervention MeSH terms: Amlexanox
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 42.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: diabetes mellitus type 2; non-alcoholic fatt liver disease; obesity

Summary:

      This study involves research about an investigational medicine called Amlexanox. The reason
      for this study is to find out how Amlexanox can improve type 2 diabetes, insulin resistance,
      obesity and non-alcoholic fatty liver disease (NAFLD). In this study, Amlexanox is considered
      to be investigational (not approved by the Food and Drug Administration [FDA]) for type 2
      diabetes, insulin resistance, obesity and non-alcoholic fatty liver disease (NAFLD). This is
      a placebo controlled study. There is a 50-50 chance that the patient may either receive the
      study drug, Amlexanox, or a placebo (sugar pill). Neither the patient or the study doctors
      will know if the patient is receiving the study drug or placebo.
    

Eligibility criteria:

        Inclusion Criteria:

          -  ≥ 18 years old at baseline.

          -  Is male, female not of childbearing potential, or meets all the following criteria if
             female of childbearing potential (including perimenopausal women who have had a
             menstrual period within one year):

               -  Not breastfeeding.

               -  Negative pregnancy test result (human chorionic gonadotropin, beta subunit
                  [βhCG]) at baseline (not applicable to hysterectomized females).

               -  Must practice and be willing to continue to practice appropriate birth control
                  (defined as a method which results in a low failure rate when use consistently
                  and correctly, such as implants, injectables, oral contraceptives, some
                  intrauterine contraceptive devices, sexual abstinence, tubal ligation, or a
                  vasectomized partner) during the entire duration of study period.

          -  Has physician-confirmed diabetes mellitus with a clear diagnosis or per ADA criteria
             with fasting glucose>126 mg/dL or HbA1c >6.4% or 2 hour GTT >200 mg/dL.

          -  BMI ≥27 and <45 kg/m2.

          -  On no medications or only on first line oral medications (such as Metformin and/or DPP
             IV inhibitors) for treatment of Type 2 diabetes mellitus with a stable regimen for >12
             weeks.

          -  Alcohol consumption of less than 40 grams/week.

          -  A liver US confirming presence of fatty infiltration of the liver.

          -  Is able to read, understand and sign the U of M IRBMED approved informed consent form
             (ICF), communicate with study physician and study team, understand and comply with
             protocol requirements.

        Exclusion Criteria:

          -  On insulin, or other injectables for treatment of Type 2 diabetes.

          -  Unable to conduct home based glucose monitoring.

          -  HbA1c <6.5% and >10.0% (set to achieve uniformity in the study population).

          -  Presence of advanced liver disease (as evidenced by abnormal synthetic function,
             abnormal PT or albumin).

          -  Evidence of other etiologies of viral hepatitis.

          -  Presence of hematologic, bone marrow and/or other abnormalities.

          -  Presence of hemoglobinopathy or other hematological abnormalities that will interfere
             with accurate measurement of HbA1c.

          -  Presence of HIV infection.

          -  Inability to give informed consent.

          -  Presence of ESRD, any type of active cancer, or >class 2 congestive heart failure
             ((New York Heart Association Functional Classification System), based on medical
             history and physical examination.

          -  Active chronic infection such as known chronic osteomyelitis or tb, etc. (may be
             transient).

          -  Creatinine >1.5 mg/dL.

          -  Proliferative diabetic retinopathy, nonproliferative retinopathy is allowed.

          -  Unable to ambulate.

          -  Clinically relevant CAD: history of stent, CABG or cardiologist confirmed angina.

          -  Any other condition in the opinion of the investigators that may impede successful
             data collection.