HypoglycemiaPhase 4HypoANS-BNCT03429946
Hypoglycemia and Autonomic Nervous System Function-B
A Phase 4 study testing Spironolactone, Hypoglycemic Hyperinsulinemic Clamp and Euglycemic Hyperinsulinemic Clamp in people with Hypoglycemia and Healthy, run by Brigham and Women's Hospital at 2 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Hypoglycemia, Healthy
- What is being tested?
- Spironolactone, Hypoglycemic Hyperinsulinemic Clamp and Euglycemic Hyperinsulinemic Clamp
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 28 participants
- Where
- 2 sitesUnited States
- Study dates
- 17 Jul 2013to 25 Nov 2025
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy volunteers
- Males and females age 18 to 55 years
Who cannot join
- 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
Show all 12Show fewer
- 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.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02115
Brigham and Women's Hospital
Boston, Massachusetts, 02115
About this study
Official title: Hypoglycemia and Autonomic Nervous System Function
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.
Read the 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
- Being tested
- Spironolactone, Placebo, Hypoglycemic Hyperinsulinemic Clamp, Euglycemic Hyperinsulinemic Clamp
- Medical subject headings
- Hypoglycemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SpironolactoneDrug
Participants will receive spironolactone 12 hours and 3 hours before the initiation of the hyperinsulinemic clamp treatment.
PlaceboDrug
Participants will receive placebo 12 hours and 3 hours before the initiation of the hyperinsulinemic clamp treatment.
Hypoglycemic Hyperinsulinemic ClampOther
Also called Hypoglycemic Hyperinsulinemic Clamp Procedure
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.
Euglycemic Hyperinsulinemic ClampOther
Also called Euglycemic Hyperinsulinemic Clamp Procedure
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Drug: Placebo; Other: Euglycemic Hyperinsulinemic Clamp |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Comparison of Day 3 muscle sympathetic nerve activity (bursts/min) assessed during hypoglycemic hyperinsulinemic clamp + placebo treatment as compared to hypoglycemic hyperinsulinemic clamp + spironolactone treatment.
Measured: Muscle sympathetic nerve activity is assessed on the 3rd day of each treatment (i.e. about 16 hours after completion of the hyperinsulinemic clamp)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Feb 2018
- Study start17 Jul 2013
- Primary completion25 Nov 2025
- Study completion25 Nov 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HypoglycemiaStudies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Participants complete all 3 arms of the study in random order.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Beth Israel Deaconess Medical Center, National Heart, Lung, and Blood Institute (NHLBI), National Center for Advancing Translational Sciences (NCATS)
- Responsible party
- Principal investigator, Gail Kurr Adler, Brigham and Women's Hospital
- Investigators
- Gail Adler, MD/PhD, Principal investigator, Brigham and Women's HospitalRoy Freeman, MD, Principal investigator, Beth Israel Deaconess Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03429946
- Sponsor's protocol ID
- 2004P001233-B
- Other IDs
- R01HL109634, K24HL103845, UL1TR001102
- Acronym
- HypoANS-B
- Status last verified
- Dec 2025
- First submitted
- 30 Jan 2018
- Last updated
- 2 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The data collected will comply with the NIH requirements for timely release and data sharing. Data will be shared in the form of publications and presentations in scientific forums. As the NIH has noted, the investigators reserve the right to keep the data restricted in order to perform the initial analyses for this grant proposal and will continue to use the data for further, but not prolonged, exclusive use. Of note, the sharing of this data will be limited by at least the following issues, some unique to this proposal and some not unique. Some of the data obtained in this study is defined to be sensitive in nature, which may restrict its ability to be shared. Data may only be shared with the approval of our IRB and is limited by HIPPA and any other regulations that may be promulgated during the course of this proposal.
Study at a glance
From the registry record, last updated by the sponsor on 2 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hypoglycemia and Autonomic Nervous System Function
- ClinicalTrials.gov ID
- NCT03429946
- Acronym / sponsor ID
- HypoANS-B / 2004P001233-B
- Conditions
- Hypoglycemia, Healthy
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Collaborators
- Beth Israel Deaconess Medical Center, National Heart, Lung, and Blood Institute (NHLBI), National Center for Advancing Translational Sciences (NCATS)
- Study start
- 17 Jul 2013 (actual)
- Primary completion
- 25 Nov 2025 (actual)
- Study completion
- 25 Nov 2025 (actual)
- First posted
- 12 Feb 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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..
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- Participants complete all 3 arms of the study in random order.
| Arm | Type | Receives |
|---|---|---|
| Hypoglycemia and Spironolactone | Active comparator | Drug: Spironolactone, Other: Hypoglycemic Hyperinsulinemic ClampParticipants 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. |
| Hypoglycemia and Placebo | Active comparator | Drug: Placebo, Other: Hypoglycemic Hyperinsulinemic ClampParticipants 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. |
| Euglycemia and Placebo | Placebo comparator | Drug: Placebo, Other: Euglycemic Hyperinsulinemic ClampParticipants 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. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Healthy volunteers
- Males and females age 18 to 55 years
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SpironolactoneParticipants will receive spironolactone 12 hours and 3 hours before the initiation of the hyperinsulinemic clamp treatment. | Drug | Hypoglycemia and Spironolactone |
| PlaceboParticipants will receive placebo 12 hours and 3 hours before the initiation of the hyperinsulinemic clamp treatment. | Drug | Euglycemia and Placebo, Hypoglycemia and Placebo |
| Hypoglycemic Hyperinsulinemic ClampAlso: Hypoglycemic Hyperinsulinemic Clamp ProcedureParticipants 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 | Hypoglycemia and Placebo, Hypoglycemia and Spironolactone |
| Euglycemic Hyperinsulinemic ClampAlso: Euglycemic Hyperinsulinemic Clamp ProcedureParticipants 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. | Other | Euglycemia and Placebo |
Primary outcome
Baroreflex Sensitivity assessed on Day 3
Time frame: Baroreflex sensitivity is assessed on the 3rd day of each treatment (i.e. about 16 hours after completion of the hyperinsulinemic clamp)
Comparison of Day 3 baroreflex sensitivity (milliseconds/mm Hg) assessed during Hypoglycemic hyperinsulinemic clamp + Placebo treatment as compared to Hypoglycemic hyperinsulinemic clamp + Spironolactone treatment.
1 secondary outcome
Muscle sympathetic nerve activity assessed on Day 3
Time frame: Muscle sympathetic nerve activity is assessed on the 3rd day of each treatment (i.e. about 16 hours after completion of the hyperinsulinemic clamp)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jan 2026.
- Individual participant dataSharing planned: Yes. The data collected will comply with the NIH requirements for timely release and data sharing. Data will be shared in the form of publications and presentations in scientific forums. As the NIH has noted, the investigators reserve the right to keep the data restricted in order to perform the initial analyses for this grant proposal and will continue to use the data for further, but not prolonged, exclusive use. Of note, the sharing of this data will be limited by at least the following issues, some unique to this proposal and some not unique. Some of the data obtained in this study is defined to be sensitive in nature, which may restrict its ability to be shared. Data may only be shared with the approval of our IRB and is limited by HIPPA and any other regulations that may be promulgated during the course of this proposal.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gail Adler, MD/PhD principal investigator
Brigham and Women's Hospital
Roy Freeman, MD principal investigator
Beth Israel Deaconess Medical Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Spironolactone, Hypoglycemic Hyperinsulinemic Clamp and Euglycemic Hyperinsulinemic Clamp in people with Hypoglycemia and Healthy, run by Brigham and Women's Hospital at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Baroreflex Sensitivity assessed on Day 3 (time frame: Baroreflex sensitivity is assessed on the 3rd day of each treatment (i.e. about 16 hours after completion of the hyperinsulinemic clamp)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jan 2026.