Hypoglycemia and Autonomic Nervous System Function- B2

Not Applicable

Active, not recruiting

• Conditions: Hypoglycemia; Type2 Diabetes
• Interventions: Other: Hyperinsulinemic Hypoglycemic Clamp

• Registration Number: NCT03422471
• Lead Sponsor: Brigham and Women's Hospital

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. .

Study Timeline

• Study Start: 2017-09-25
• Study First Submitted: 2018-01-30
• Study First Submitted QC: 2018-01-30
• Study First Posted: 2018-02-05
• Status Verified: 2022-07
• Last Update Submitted: 2022-07-18
• Last Update Posted: 2022-07-20
• Primary Completion: 2023-12-28
• Study Completion: 2024-10-28

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 14

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Hypoglycemia	Hyperinsulinemic Hypoglycemic Clamp	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.

Primary Outcome Measures

Name	Time	Method
Modified Oxford Method Assessment of Baroreflex Function	Time 0 and 16 hours after hyperinsulinemic hypoglycemic clamps	Change in baroreflex sensitivity between the first assessment (pre-AM clamp on Day 1) and the final assessment (AM of Day 2, about 16 hours after the PM clamp)

Trial Locations

Locations (1)

Brigham and Women's Hospital; 🇺🇸 Boston, Massachusetts, United States