Hypoglycemia and Autonomic Nervous System Function- B2 (HypoANS-B2)

Mass General Brigham

Status: Active, not recruiting

Conditions: Hypoglycemia; Type2 Diabetes

Treatments: Other: Hyperinsulinemic Hypoglycemic Clamp

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT03422471

K24HL103845 (U.S. NIH Grant/Contract)

T32HL007609 (U.S. NIH Grant/Contract)

R01HL111465 (U.S. NIH Grant/Contract)

UL1TR001102 (U.S. NIH Grant/Contract)

2004P001233-B2

Details and patient eligibility

About

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

Full 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. .

Enrollment: 14 estimated patients

Sex: All

Ages: 18 to 55 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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14 participants in 1 patient group

Hypoglycemia

Experimental group

Description:

Participants are exposed to two 90 minute episodes of hypoglycemia (50 mg/dl) through a hyperinsulinemic hypoglycemic clamp. Baroreflex sensitivity will be assessed before, during, and 16 hours after the hypoglycemia.

Treatment:

Other: Hyperinsulinemic Hypoglycemic Clamp