Clinical trial NCT03429946: Hypoglycemia and Autonomic Nervous System Function-B
Official title: Hypoglycemia and Autonomic Nervous System Function
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Hypoglycemia
Healthy
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: 2018-02-12
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Participants complete all 3 arms of the study in random order.
Primary purpose: BASIC_SCIENCE

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.

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..

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Baroreflex Sensitivity assessed on Day 3
timeFrame: Baroreflex sensitivity is assessed on the 3rd day of each treatment (i.e. about 16 hours after completion of the hyperinsulinemic clamp)
Secondary outcomes:
measure: Muscle sympathetic nerve activity assessed on Day 3
timeFrame: Muscle sympathetic nerve activity is assessed on the 3rd day of each treatment (i.e. about 16 hours after completion of the hyperinsulinemic clamp)
Other outcomes:
Locations:
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
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: