NCT03429946

Hypoglycemia and Autonomic Nervous System Function-B

Hypoglycemia and Autonomic Nervous System Function

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 28 (actual)
• Sponsor: Brigham and Women's Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 55 Years
• Healthy volunteers: Accepted

Summary

This study tests the hypothesis that, compared to prior normal blood sugar, prior low blood sugar impairs cardiovascular autonomic function. The proposed studies will also test the hypothesis that the effects of prior low blood sugar on cardiovascular autonomic function are blocked by administration of a mineralocorticoid receptor antagonist.

Detailed description

This study involves three interventions, which are performed in random order. Each intervention involves a 3-day inpatient visit. There is a space of 1-3 months between interventions. The three interventions are: 1) placebo with a hyperinsulinemic euglycemic clamp, 2) spironolactone with a hyperinsulinemic hypoglycemic clamp, or 3) placebo with a hyperinsulinemic hypoglycemic clamp. Each 3-day inpatient visit includes the following. On Day 1, autonomic testing is performed. Autonomic testing includes assessment of Baroreflex Sensitivity (BRS). BRS is assessed using the Modified Oxford procedure, which involves sequential administration of nitroprusside and phenylephrine while measuring heart rate and beat to beat blood pressure with a finapress and assessing Muscle Sympathetic Nerve Activity (MSNA). MSNA is measured using microelectrodes placed near the peroneal nerve. On Day 2, hyperinsulinemic clamps are performed with pre-treatment with either placebo or spironolactone. Modified Oxford Procedures are performed prior to and during each clamp on Day 2. On Day 3, the autonomic testing performed on Day 1 is repeated..

Conditions

• Hypoglycemia
• Healthy

Interventions

Type	Name	Description
DRUG	Spironolactone	Participants will receive spironolactone 12 hours and 3 hours before the initiation of the hyperinsulinemic clamp treatment.
DRUG	Placebo	Participants will receive placebo 12 hours and 3 hours before the initiation of the hyperinsulinemic clamp treatment.
OTHER	Hypoglycemic Hyperinsulinemic Clamp	Participants undergo two 120-minute hypoglycemic (50 mg/dL) hyperinsulinemic clamps - an AM clamp from about 9 am to 11 am and a PM clamp from 1 pm to 3 pm on Day 2 of a 3-Day study visit. Modified Oxford Procedure is performed in duplicate at six time points - on Day 1, before the AM hyperinsulinemic clamp, during the AM hyperinsulinemic clamp, before the PM hyperinsulinemic clamp, during the PM hyperinsulinemic clamp, and on Day 3. The Modified Oxford procedure is performed to calculate baroreflex sensitivity.
OTHER	Euglycemic Hyperinsulinemic Clamp	Participants undergo two 120-minute euglycemic (90 mg/dL) hyperinsulinemic clamps - an AM clamp from about 9 am to 11 am and a PM clamp from 1 pm to 3 pm on Day 2 of a 3-Day study visit.Modified Oxford Procedure is performed in duplicate at six time points - on Day 1, before the AM hyperinsulinemic clamp, during the AM hyperinsulinemic clamp, before the PM hyperinsulinemic clamp, during the PM hyperinsulinemic clamp, and on Day 3. The Modified Oxford procedure is performed to calculate baroreflex sensitivity.

Timeline

• Start date: 2013-07-17
• Primary completion: 2025-11-25
• Completion: 2025-11-25
• First posted: 2018-02-12
• Last updated: 2026-01-02

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study