Hypoglycemia and Autonomic Nervous System Function-B

NCT03429946 | Completed Phase 4 DMC FDA Drug

• 4 other identifiers: 2004P001233-BR01HL109634K24HL103845UL1TR001102
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Hypoglycemia; Healthy

Outcome Measures

Primary Outcomes (1)

• Baroreflex Sensitivity assessed on Day 3

  Comparison of Day 3 baroreflex sensitivity (milliseconds/mm Hg) assessed during Hypoglycemic hyperinsulinemic clamp + Placebo treatment as compared to Hypoglycemic hyperinsulinemic clamp + Spironolactone treatment.

  Baroreflex sensitivity is assessed on the 3rd day of each treatment (i.e. about 16 hours after completion of the hyperinsulinemic clamp)

Secondary Outcomes (1)

• Muscle sympathetic nerve activity assessed on Day 3

  Muscle sympathetic nerve activity is assessed on the 3rd day of each treatment (i.e. about 16 hours after completion of the hyperinsulinemic clamp)

Study Arms (3)

Hypoglycemia and Spironolactone

ACTIVE COMPARATOR

Participants undergo two 120-minute hypoglycemic hyperinsulinemic clamp procedures (50 mg/dL) - 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. Participants receive two doses of 100 mg of spironolactone - one dose 12 hours and one dose 3 hours before the first clamp starts. 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.

Drug: Spironolactone; Other: Hypoglycemic Hyperinsulinemic Clamp

Hypoglycemia and Placebo

ACTIVE COMPARATOR

Participants undergo two 120-minute hypoglycemic hyperinsulinemic clamp procedures (50 mg/dL) - 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. Participants receive two doses of placebo - one dose 12 hours and one dose 3 hours before the first clamp starts. 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.

Drug: Placebo; Other: Hypoglycemic Hyperinsulinemic Clamp

Euglycemia and Placebo

PLACEBO COMPARATOR

Participants undergo two 120-minute euglycemic hyperinsulinemic clamp procedures (90 mg/dL) - 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. Participants receive two doses of placebo - one dose 12 hours and one dose 3 hours before the first clamp starts. 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.

Drug: Placebo; Other: Euglycemic Hyperinsulinemic Clamp

Interventions

Spironolactone DRUG

Participants will receive spironolactone 12 hours and 3 hours before the initiation of the hyperinsulinemic clamp treatment.

Hypoglycemia and Spironolactone

Placebo DRUG

Participants will receive placebo 12 hours and 3 hours before the initiation of the hyperinsulinemic clamp treatment.

Euglycemia and Placebo; Hypoglycemia and Placebo

Hypoglycemic Hyperinsulinemic Clamp OTHER

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.

Also known as: Hypoglycemic Hyperinsulinemic Clamp Procedure

Hypoglycemia and Placebo; Hypoglycemia and Spironolactone

Euglycemic Hyperinsulinemic Clamp OTHER

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.

Also known as: Euglycemic Hyperinsulinemic Clamp Procedure

Euglycemia and Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy volunteers
• Males and females age 18 to 55 years

You may not qualify if:

• Pregnancy
• Lactation
• Clinically evident coronary artery, cerebrovascular, or peripheral vascular disease, or presence of systemic illness that might affect autonomic function. Such illnesses include diabetes mellitus, congestive heart failure, hypertension, 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.
• Use of medications other than thyroxine
• Known hypersensitivity to nitroglycerin, nitroprusside and/or phenylephrine.
• Blood pressure \> 140/90 mmHg
• 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.

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• Beth Israel Deaconess Medical Center: collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• National Center for Advancing Translational Sciences (NCATS): collaborator

Study Sites (2)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Hypoglycemia

Interventions

Spironolactone

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Lactones; Organic Chemicals; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Gail Adler, MD/PhD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

• Roy Freeman, MD

  Beth Israel Deaconess Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Investigator performing the clamp studies is only aware of the type of clamp - euglycemic versus hypoglycemic - but not aware of placebo versus spironolactone.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Participants complete all 3 arms of the study in random order.

Study Record Dates

• First Submitted: January 30, 2018
• First Posted: February 12, 2018
• Study Start: July 17, 2013
• Primary Completion: November 25, 2025
• Study Completion: November 25, 2025
• Last Updated: January 2, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Time Frame: Data will be shared after completion of study and initial publications which we anticipate to be within 18 months of the final participant completing the study protocol.
• Access Criteria: Access to data must be approved by the IRB at our institution.

Locations

US (2)