Amlexanox for Type 2 Diabetes and Obesity
Condition: Diabetes Mellitus Type 2; Non Alcoholic Fatty Liver Disease; Obesity
MeSH terms: Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Diabetes Mellitus; Obesity; Diabetes Mellitus, Type 2
Intervention: Amlexanox
Intervention MeSH terms: Amlexanox
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 7.0
Sex: All
Minimum age: 18 Years
Maximum age: 59 Years
Healthy volunteers: No
Keywords: diabetes mellitus type 2; non alcoholic fatty liver disease; obesity; amlexanox

Summary:

      This study involves the use of a research drug, Amlexanox, for the treatment of type 2
      diabetes, insulin resistance, obesity and non-alcoholic fatty liver disease (NAFLD).
      Amlexanox is taken orally in a pill three times a day. The investigators plan to continue
      therapy for a period of 12 weeks followed by a follow-up 4 weeks after therapy ends. The
      investigators will evaluate the changes in metabolic parameters (e.g. blood cholesterol,
      liver function, insulin resistance) and body composition characteristics (e.g. the pattern of
      fat distribution in the body). Seven eligible subjects in this study will also be evaluated
      for a change in liver disease by a liver biopsy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  ≥ 18 years old at baseline and <60 years of age.

          -  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 or or
             pre-diabetes with fasting glucose >100 mg/dL (n= up to 8)

          -  BMI ≥27 and <36 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, sulfonylurea or other injectables for treatment of type 2 diabetes

          -  Unable to conduct home based glucose monitoring

          -  HbA1c>9.5%

          -  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.