Diabetes Mellitus Type 2, Non Alcoholic Fatty Liver Disease, Obesity
Conditions
Keywords
diabetes mellitus type 2, non alcoholic fatty liver disease, obesity, amlexanox
Brief 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.
Interventions
DRUGAmlexanox
Sponsors
University of Michigan
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| HbA1c | 12 weeks | Change in HbA1c from baseline to 12 weeks as shown by mean increase or decrease of HbA1c where decreased values represent better health |
| Hepatic Steatosis by MRI | 12 weeks | change in hepatic steatosis from baseline to 12 weeks: MRI Liver fat percentage as shown by mean difference |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Weight | 12 weeks | Change in weight (Kg) from baseline to 12 weeks as shown by mean difference, where lower weights represent healthier outcomes |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Amlexanox Amlexanox | 7 |
| Total | 7 |
Baseline characteristics
| Characteristic | Amlexanox |
|---|---|
| A1C | 7.9 percent of total hemoglobin |
| Age, Continuous | 60 years |
| Hepatic Steatosis by MRI | 7.5 percentage of fat in liver |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 6 Participants |
| Region of Enrollment United States | 7 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 3 Participants |
| Weight | 97.6 kg |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 7 |
| other Total, other adverse events | 7 / 7 |
| serious Total, serious adverse events | 0 / 7 |
Outcome results
Primary
HbA1c
Change in HbA1c from baseline to 12 weeks as shown by mean increase or decrease of HbA1c where decreased values represent better health
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Amlexanox | HbA1c | 0 percentage of total hemoglobin |
Primary
Hepatic Steatosis by MRI
change in hepatic steatosis from baseline to 12 weeks: MRI Liver fat percentage as shown by mean difference
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Amlexanox | Hepatic Steatosis by MRI | -2.2 percentage of liver mass |
Secondary
Weight
Change in weight (Kg) from baseline to 12 weeks as shown by mean difference, where lower weights represent healthier outcomes
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Amlexanox | Weight | -2.2 kg |