Clinical trial NCT03422471: Hypoglycemia and Autonomic Nervous System Function- B2
Official title: Hypoglycemia and Autonomic Nervous System Function
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Hypoglycemia
Type2 Diabetes
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
Collaborators: name: Beth Israel Deaconess Medical Center
name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2018-02-05
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: We will study the effect of hypoglycemia (low blood sugar) on baroreflex sensitivity in participants with well controlled type 2 diabetes.

Detailed description: Participants are admitted for two days and two nights to an inpatient clinical research center for performance of study procedures. On Day 1, two hyperinsulinemic hypoglycemic (50 mg/dl) clamps are performed - an AM clamp from about 9 to 11 am and a PM clamp from about 1 to 3 pm.. Modified Oxford procedures are performed in duplicate at five time points -- before the AM clamp, during the AM clamp, before the PM clamp, during the PM clamp, and the morning of Day 2 (about 16 hrs after completion of the the PM clamp). The Modified Oxford procedure involves the sequential intravenous administration of nitroprusside and phenylephrine with assessment of blood pressure and heart rate by finapress. Baroreflex sensitivity is the relationship of changes in heart rate to changes in blood pressure. .

Eligibility criteria: Inclusion Criteria:

* Males and females age 18 to 55 years
* Type 2 Diabetes Mellitus controlled by diet, exercise and non-insulin glycemic control agents (metformin, thiazolidinediones, sulfonylureas, dipeptidyl peptidase-4 inhibitors, sodium-glucose co-transporter 2 inhibitors, alpha-glucosidase inhibitors or glucagon-like peptide-1 receptor agonist) or basal insulin at doses less than or equal to 0.3 units/ kg per day.

Exclusion Criteria:

* Hemoglobin A1c \> 9% for type 2 diabetes
* Recurrent hypoglycemic episodes within the past month
* BMI \< 25 or \> 42 (Type 2 diabetes only)
* Pregnancy
* Lactation
* Clinically significant coronary artery, cerebrovascular, or peripheral vascular disease, or presence of systemic illness that might affect autonomic function. Such illnesses include congestive heart failure, renal, pulmonary, hepatic disease, anemia, malignancies, untreated thyroid disease, and alcoholism.
* Current major depressive illness
* In all subjects, any individuals on oral, injected, inhaled or topical corticosteroids within the last year or oral contraceptives within the past 3 months will be excluded.
* Known hypersensitivity to nitroglycerin, nitroprusside and/or phenylephrine.
* Blood pressure \> 160/100 mmHg (applies to participants with T2 diabetes)
* Creatinine \> 1.5 mg/dL
* Serum potassium \>5.2 mmol/L
* Estimated GFR \< 50 mL/min
* Use of Viagra, Cialis, and similar drugs within 72 hours of admission.
* Use of beta-blockers or mineralocorticoid receptor antagonists

Primary outcomes:
measure: Modified Oxford Method Assessment of Baroreflex Function
timeFrame: Time 0 and 16 hours after hyperinsulinemic hypoglycemic clamps
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: Gail Adler, MD/PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Beth Israel Deaconess Medical Center
name: Roy Freeman, MD
role: PRINCIPAL_INVESTIGATOR
References: