Randomized Study of Yohimbine Treatment for Type 2 Diabetes Patients Carrying a Specific Genetic Risk Variant

Study Overview
=================
Brief Summary
-----------------
The investigators have recently discovered a genetic variant in an adrenergic receptor that leads to increased risk for type 2 diabetes. The investigators have also seen that blockers of that receptor improves impaired insulin secretion in animals. The investigators will now test the blocker in patients with type 2 diabetes with or without the risk variant in an effort to make diabetes treatment more individualized.

Detailed Description
-----------------
We have recently discovered a genetic variant in an adrenergic receptor that leads to increased risk for type 2 diabetes. We have also seen that blockers of that receptor improves impaired insulin secretion in animals. We will now test the blocker in patients with type 2 diabetes with or without the risk variant in an effort to make diabetes treatment more individualized. Patients will receive two different doses of the blocker and the effect will be measured with oral glucose tolerance tests. The study is a randomized placebo-controlled study.

Official Title
-----------------
Randomized Study of Yohimbine Treatment for Type 2 Diabetes Patients Carrying a Specific Genetic Risk Variant

Conditions
-----------------
Type 2 Diabetes

Intervention / Treatment
-----------------
* Drug: Yohimbine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: type 2 diabetes informed consent age 18-70, for females only postmenopausal Exclusion Criteria: heart disease anxiety disorder antidiabetic treatment other than metformin adrenergic blockers ulcus allergy to any component in the capsules

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Placebo first then yohimbine<br>placebo first, then yohimbine | Drug: Yohimbine<br>* Yohimbine capsule<br>|
| Active Comparator: Yohimbine first then placebo<br>Yohimbine first then placebo | Drug: Yohimbine<br>* Yohimbine capsule<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin Secretion | insulin secretion will be measured (nMole) in response to an oral glucose tolerance test. Patients will receive the capsules 1 h before the glucose test, and the insulin levels 30 minutes after the oral glucose will be used as a primary outcome measure. The insulin levels at the highest tolerated dose of yohimbine will be used. | 30 minutes after oral glucose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucose | Plasma glucose will be measure (mMole) in response to an oral glucose tolerance test. Patients will receive the capsules 1 h before the glucose test, and the glucose levels 30 minutes after the oral glucose will be used as a secondary outcome measure. The glucose levels at the highest tolerated dose of yohimbine will be used. | 30 minutes after oral glucose | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
genetics, type 2 diabetes, insulin secretion