CharacterIzation of Adult Onset Autoimmune Diabetes

CharacterIzation of Adult Onset Autoimmune Diabetes

Sponsors

Lead sponsor: Translational Research Institute for Metabolism and Diabetes, Florida

Source Translational Research Institute for Metabolism and Diabetes, Florida
Brief Summary

The purpose of the study is to identify new biomarkers of Adult Onset Autoimmune Diabetes (AOnAD).

Overall Status Recruiting
Start Date July 8, 2019
Completion Date June 2021
Primary Completion Date June 2021
Study Type Observational
Primary Outcome
Measure Time Frame
Blood collection Screening Visit and Day 1
Enrollment 40
Condition
Intervention

Intervention type: Other

Intervention name: Mixed Meal Test

Description: a standard liquid mixed meal will be administered to the participant. The test meal with 1 kcal/ml and with the following caloric distribution Protein: 25%, Carbohydrate: 53%, Fat: 22% is given at a dose of 6 mL per kilogram body weight. Maximum dose is 360 mL and it will be ingested over 5 minutes. Blood samples will be taken 10 min prior to ingestion (t=-10), at baseline (t = 0), and at 15, 30, 60, 90, and 120 minutes.

Intervention type: Other

Intervention name: Dual Energy X-Ray Absorptiometry (DEXA)

Description: DEXA Scans will be performed to obtain body composition measures (body fat and estimated muscle mass) using a General Electric (GE) Lunar iDXA whole-body scanner.

Intervention type: Procedure

Intervention name: Adipose Tissue Biopsy

Description: The abdominal skin 6-10 cm lateral to the umbilicus will be cleansed with chlorhexidine. A sterile drape is placed, and the skin and adipose tissue will be anesthetized using Lidocaine. A 3-4 mm Mercedes Liposuction cannula will be inserted for aspiration of up to 2g of adipose tissue.

Eligibility

Sampling method: Non-Probability Sample

Criteria:

Inclusion Criteria:

Type 1 Diabetes (T1D)

- age 18-35 years

- age at diagnosis 13 to 30 years

- Body Mass Index (BMI) 25 to 35 kg/m2 with a stable body weight (±3 kg in the past 6 months)

- diagnosis of T1D according to American Diabetes Association (ADA) criteria continuously requiring insulin for survival (if in doubt, diagnosis can be confirmed by positivity of 2 or more IAAb* at time of diagnosis, at any time or at time of recruitment)

- diabetes diagnosis performed within the previous 5 years,

- requiring insulin continuously since diagnosis to prevent ketosis

- Fasting C-peptide levels < 0.3 nmol/l

Type 2 Diabetes (T2D)

- age 40-75 years

- age at diagnosis 40 to 70 years

- BMI 25 to 35 kg/m2 with a stable body weight (±3 kg in the past 6 months)

- diagnosis of diabetes according to ADA criteria

- Diabetes diagnosis performed within the previous 5 years

- Not requiring insulin

- Fasting C-peptide levels > 0.3 nmol/l

Adult Onset Autoimmune Diabetes/Latent Autoimmune Diabetes of Adults (AOnAD/LADA)

- age 40-75 years

- age at diagnosis 40 to 70 years

- BMI 25 to 35 kg/m2 with a stable body weight (±3 kg in the past 6 months)

- diagnosis of diabetes according to ADA criteria

- fasting C-peptide > 0.3 nmol/l

- positive for at least one islet autoantibody (IAAb* - at time of diagnosis, at any time or at time of recruitment)

- not requiring insulin or, if on insulin, treatment started at least 6 months after diagnosis

Healthy Normal Volunteers (HNV)

- age 40-75 years

- BMI 25 to 35 kg/m2 with a stable body weight (±3 kg in the past 6 months)

- No personal history of diabetes according to ADA criteria

- No history of diabetes in first degree relatives (FDRs)

- Fasting C-peptide levels > 0.3 nmol/l

- IAAbs are Insulin AutoAntibodies (IAA), Thyrosine phosphatase IA-2 Antibodies (IA-2 Ab), Glutamic Acid Decarboxylase Antibodies (GAD Ab), Zinc Transporter 8 Antibodies (ZnT8 Ab), Islet Cell Antibodies (ICA).

Exclusion Criteria:

- For T2D participants: treatment with insulin or with thiazolidinediones (TZDs).

- For T1D and AOnAD/LADA participants: treatment with TZDs.

- Presence of unstable cardiovascular disease (unstable angina, myocardial infarction or coronary revascularization within 6 months, clinically significant abnormalities on EKG, presence of cardiac pacemaker, implanted cardiac defibrillator)

- Evidence of acute or chronic liver disease even if asymptomatic (AST or ALT >2.5 times the upper limit of normal)

- Kidney disease (creatinine >1.6 mg/dl or estimated GFR<60 ml/min)

- Triglycerides >500 mg/dl, LDL >200 mg/dl

- Uncontrolled hypertension (Blood Pressure BP>160 mmHg systolic or >100 mmHg diastolic)

- Recent important weight loss (>3 kg in 3 months)

- History of drug or alcohol abuse (> 3 drinks per day) within the last 5 years.

- History of cancer within the last 5 years (skin cancers, with the exception of melanoma, may be acceptable).

- History of organ transplant.

- History of bariatric surgery

- Bleeding or coagulation disorders requiring chronic use of blood thinners.

- Current treatment with blood thinners or antiplatelet medications that cannot be safely stopped for study procedures

- History of chronic pancreatitis or pancreatic surgery

- Acute or chronic infections

- History of HIV, active Hepatitis B or C, or Tuberculosis.

- Anemia (hemoglobin <12 g/dl in men, <11 g/dl in women) or other chronic hematology disorders.

- Use of any medications known to influence glucose, fat and/or energy metabolism within the last 3 months (e.g., growth hormone therapy, glucocorticoids [steroids], etc.) other than the treatment for diabetes

- Thyroid dysfunction. Participants with a Thyroid Stimulating Hormone TSH > 10 µ IU or less than 0.4 µ IU are excluded. Participants on thyroid replacement medication or on antithyroid drugs may be enrolled providing they have been on a stable dose of medication for at least 6 weeks prior to screening and their TSH is within the range specified above.

- Severe asthma or chronic obstructive pulmonary disease

- Initiation or change in hormone replacement therapy within the past 3 months (including, but not limited to birth control or estrogen replacement therapy)

- Cushing's disease or syndrome

- Drugs that affect immune, weight or metabolic function, including but not limited to: oral corticosteroids, oral or injectable anti-obesity medications. Drugs for dyslipidemia (statins, ezetimibe, etc.) and a daily full strength or baby aspirin for atherosclerosis prevention will be allowed, provided patients have been on stable doses for at least 6 weeks prior to screening and that aspirin could be safely temporarily stopped for the study

- Weight >450 lbs. (This is Dual X-ray Absorptiometry (DEXA) table weight limit)

- Gastrointestinal disorders associated with malabsorption.

- Pregnant or nursing females or females less than 6 months postpartum from the scheduled date of collection.

- Had major surgery within 4 weeks prior to the pre-trial (screening) visit

- Participation in studies involving investigational drug(s) within 30 days prior to Screening Visit 1

- Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 56 days prior to Screening Visit

- Allergies to milk derived or soy derived products, lactose intolerance (due to the composition of the standard liquid meal that will be used for the test)

- Allergies and reactions to lidocaine.

- History of eating disorders

- Psychiatric disease prohibiting adherence to study protocol

- Unable to provide a reliable informed consent

- Presence of any condition that, in the opinion of the investigator and clinical team, compromises participant safety or data integrity or the participant's ability to complete study visits

Gender: All

Minimum age: 18 Years

Maximum age: 75 Years

Healthy volunteers: Accepts Healthy Volunteers

Overall Official
Last Name Role Affiliation
Anna Casu Principal Investigator Study Principal Investigator
Overall Contact

Last name: Recruitment Department

Phone: 407-303-7100

Email: [email protected]

Location
facility status contact Translational Research Institute for Metabolism and Diabetes Recruitment Department 407-303-7100 [email protected]
Location Countries

United States

Verification Date

July 2019

Responsible Party

Responsible party type: Sponsor

Has Expanded Access No
Condition Browse
Arm Group

Arm group label: Adult Onset Autoimmune Diabetes/Latent Autoimmune Diabetes

Arm group label: Type 2 Diabetes

Arm group label: Type 1 Diabetes

Arm group label: Healthy Normal Volunteers (HNV)

Acronym CIAO
Patient Data No
Study Design Info

Observational model: Other

Time perspective: Cross-Sectional

Source: ClinicalTrials.gov