Thyroid Hormone to Induce Non-Insulin Mediated Glucose Disposal in People With Insulin Receptor Mutations
- Insulin receptor mutation causes high blood sugars and sometimes diabetes complications. Researchers want to see if thyroid hormone helps.
- To see if thyroid hormone treatment changes how the body handles sugar in people with insulin receptor mutation and improves blood sugar in people with diabetes.
- People ages 12 65 with an insulin receptor mutation.
- Study part 1:19-day clinic stay. Participants will be monitored for 4 days. Then for 15 days they will take a thyroid hormone pill 3 times a day. Participants will have:
- Blood tests.
- Heart rate and skin temperature monitored.
- All their food provided.
- Two 5-hour sessions in a special room. They will wear special clothes and sometimes sit still.
- Two small tubes inserted in veins. One will deliver tiny amounts of sugar and fat with a non-radioactive tracer. Participants will also drink water with a tracer. The other tube will collect blood.
- A sweet drink. Participants may have finger stick blood sugar tests.
- Glucose-monitoring device inserted into body fat for two 24-hour periods.
- Adults may have samples of fat and muscle taken.
- Heart ultrasound.
- PET-CT scan in a machine. An intravenous catheter will be placed in an arm vein. A small amount of radioactive substance will be injected.
- DEXA scan of body fat and bone density.
- Participants with poorly controlled diabetes will then take thyroid hormone at home for 6 months. They will have blood drawn and sent to the study team monthly.
- After about 3 months, they will have an overnight visit. After 6 months, they will have a 4-day visit.
Abnormal Glucose Metabolism
|Study Design:||Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Thyroid Hormone to Induce Non-Insulin Mediated Glucose Disposal in Patients With Insulin Receptor Mutations|
- Thyroid hormone effects on glucose disposal [ Time Frame: 2 weeks ]
- Thyroid hormone effects on hemoglobin A1C [ Time Frame: 6 months ]
- Quantification of fractional gluconeogenesis and glycogenolysis using isotopic tracers [ Time Frame: 2 weeks, 6 months ]
- Thyroid hormone effects on glucose area under the curve using 7 point daily plasma glucose measurement, continuous interstitial fluid glucose monitoring, and oral glucose tolerance testing [ Time Frame: 2 weeks, 6 months ]
- Thyroid hormone effects on tissue-specific glucose disposal in the fasting state in brown adipose tissue, white adipose tissue, and muscle using PET/CT [ Time Frame: 2 weeks ]
|Study Start Date:||April 2015|
|Estimated Study Completion Date:||November 2020|
|Estimated Primary Completion Date:||November 2017 (Final data collection date for primary outcome measure)|
Patients with mutations of the insulin receptor have extreme insulin resistance. This frequently results in diabetes in childhood that is extremely difficult to manage with conventional diabetes therapies, including insulin at doses 10-50 fold higher than usual. Poorly controlled diabetes, in tum, leads to microvascular complications (e.g. blindness) and early death. Hyperthyroidism, whether endogenous (e.g. Graves' disease) or exogenous, increases energy expenditure, activates brown adipose tissue, and enhances skeletal muscle perfusion, leading to enhanced glucose disposal. In a single patient with mutation of the insulin receptor and poorly controlled diabetes despite maximal therapy, iatrogenic mild hyperthyroidism for treatment of thyroid cancer resulted in normalization of glycemia control, suggesting that thyroid hormone treatment could have therapeutic benefit in this rare disease.
The purpose ofthis study is to determine if treatment with thyroid hormone will increase glucose disposal in patients with mutations ofthe insulin receptor, and thereby improve glycemia control. The hypotheses to be tested are:
- Thyroid hormone will increase whole-body glucose disposal in patients with insulin receptor mutations.
- This increased glucose disposal will be mediated via increased glucose uptake in BAT and muscle.
- Increases in glucose disposal will result in improved glycemia control.
This study is a non-randomized pre-post design, conducted in two sequential parts. Part 1 is a short-term (2 week) proof-of-principle study to test whether thyroid hormone will increase glucose disposal in patients with insulin receptor mutations (with or without diabetes), and the mechanisms by which increased glucose disposal occurs. Part 2 is a longer term (6 month) therapeutic study to test whether thyroid hormone will result in improved glycemia control in diabetic patients with insulin receptor mutations.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02457897
|Contact: Rebecca J Brown, M.D.||(301) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL) 800-411-1222 ext TTY8664111010 email@example.com|
|Principal Investigator:||Rebecca J Brown, M.D.||National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)|