Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Beth Israel Deaconess Medical Center | OTHER |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Models of stress such as hypoglycemia have identified that stress results the next day in decreased baroreflex sensitivity. This project will test the hypothesis that these delayed changes in autonomic nervous system function are secondary to a rise in ACTH. The investigators will infuse cosyntropin versus placebo in a double-blind, crossover study in healthy adults and measure the delayed effects on the autonomic system as measured by cardiovagal baroreflex sensitivity.
Stress has complex effects on the body's physiology. Models of stress such as hypoglycemia have identified that stress activates the hypothalamic-pituitary-adrenal (HPA) axis and sympathoadrenal system acutely. Additionally, there are delayed effects of prior exposure to hypoglycemia. The day after being exposed to a hypoglycemic stimulus there are: 1) decreases in the catecholamine release to a new hypoglycemic stress; 2) decreases in the muscle sympathetic nerve activity (MSNA) response to either a new hypoglycemic challenge or transient hypotension; 3) decreases in cardiac vagal baroreflex sensitivity (BRS); and 4) increases in sensitivity to thermal pain and altered temporal summation (decreased tolerance to a repeated minimally painful stimulus). This project will test the hypothesis that these delayed changes in autonomic nervous system function are secondary to a rise in ACTH that occurs in response to stress.
Primary Aim. Infusion of ACTH (cosyntropin) will lead the next day to decreased cardiovagal baroreflex sensitivity in healthy subjects.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cosyntropin | Active Comparator | Subjects will receive cosyntropin infusion at 70 mcg/hr for two sessions of 2.5 hours each on day 2 of a three day admission to our research center. |
|
| Normal saline (Placebo) | Placebo Comparator | Subjects will receive normal saline infusion for two sessions of 2.5 hours each on day 2 of a three day admission to our research center. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cosyntropin | Drug | Subjects will receive cosyntropin at 70 mcg/hr for two sessions of 2.5 hours each on day 2 of a three day admission to our research center. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Cardiovagal Baroreflex Sensitivity (Modified Oxford Technique) | Cardiovagal baroreflex sensitivity will be measured with the Modified Oxford Technique before, during, and after drug infusions, to evaluate the effects of cosyntropin infusions. | Baseline, 4-hours after infusion, 24-hours after infusion |
Not provided
| Measure | Description | Time Frame |
|---|---|---|
| Pain (Quantitative Sensory Testing Using a Thermal Pain Testing Device) | Alterations in pain sensing will be evaluated pre and post with quantitative sensory testing using a thermal pain testing device, to evaluate the delayed effect of cosyntropin infusions. | 1 day after ACTH |
| Hippocampal Memory (Paired Associative Learning Task) |
Inclusion Criteria:
Subjects must be currently healthy, BMI 18-32 kg/m2, and not be on any medications.
This study will recruit men and women. Due to concerns about estrogen's effects on hormone levels and possible contributions of menstrual symptoms on pain sensing thresholds, we will schedule the inpatient studies to avoid the early follicular phase in normally cycling women.
Subjects must have normal laboratory values for:
Exclusion Criteria:
We will exclude individuals with:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Gail Adler, MD, PhD | Brigham and Women's Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Brigham and Women's Hospital | Boston | Massachusetts | 02115 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34788228 | Derived | Zaheer S, Meyer K, Easly R, Bayomy O, Leung J, Koefoed AW, Heydarpour M, Freeman R, Adler GK. Effect of adrenocorticotropic hormone infusion on circulating sclerostin levels. Endocr Connect. 2021 Dec 14;10(12):1607-1614. doi: 10.1530/EC-21-0263. | |
| 32761088 | Derived | van der Boom T, Jia C, Lefrandt JD, Connelly MA, Links TP, Tietge UJF, Dullaart RPF. HDL Cholesterol Efflux Capacity is Impaired in Severe Short-Term Hypothyroidism Despite Increased HDL Cholesterol. J Clin Endocrinol Metab. 2020 Sep 1;105(9):e3355-62. doi: 10.1210/clinem/dgaa411. |
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Placebo (Period 1)/Washout (Period 2)/Cosyntropin (Period 3) | Period 1: Subjects will receive a placebo infusion for two sessions of 2.5 hours each on day 2 of their first three day admission to our research center. Period 2: Washout for one month Period 3: Subjects will receive cosyntropin infusion at 70 mcg/hr for two sessions of 2.5 hours each on day 2 of their second three day admission to our research center. |
| FG001 | Cosyntropin (Period 1)/Washout (Period 2)/ Placebo (Period 3) | Period 1: Subjects will receive a cosyntropin infusion at 70 mcg/hr for two sessions of 2.5 hours each on day 2 of their first three day admission to our research center. Period 2: Washout for one month Period 3: Subjects will receive a placebo infusion for two sessions of 2.5 hours each on day 2 of their second three day admission to our research center. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 1 (Placebo or Cosyntropin) |
|
| ||||||||||||||||||
| Washout (Period 2) |
| |||||||||||||||||||
| Period 3 (Placebo or Cosyntropin) |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Healthy Control |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Cardiovagal Baroreflex Sensitivity (Modified Oxford Technique) | Cardiovagal baroreflex sensitivity will be measured with the Modified Oxford Technique before, during, and after drug infusions, to evaluate the effects of cosyntropin infusions. | Posted | Mean | Standard Deviation | ms/mmHg | Baseline, 4-hours after infusion, 24-hours after infusion |
|
Not provided
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | 0 | 22 |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| vomiting | Gastrointestinal disorders | Subject vomited during study, likely due to GI illness. |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Gail Kurr Adler | Brigham and Women's Hospital | (617) 732-8742 | gadler@bwh.harvard.edu |
Not provided
| ID | Term |
|---|---|
| D003366 | Cosyntropin |
| D000324 | Adrenocorticotropic Hormone |
| D000077330 | Saline Solution |
| ID | Term |
|---|---|
| D053486 | Melanocortins |
| D011333 | Pro-Opiomelanocortin |
| D007028 | Hypothalamic Hormones |
| D036361 | Peptide Hormones |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| Placebo | Drug | Subjects will receive placebo (normal saline infusion) for two sessions of 2.5 hours each on day 2 of a three day admission to our research center. |
|
|
Hippocampal memory will be evaluated pre and post with a paired associative learning task. Face Name Associative Memory Exam (FNAME) composite score on a scale from 0-36, with 36 being the best possible score. |
| 1 day after ACTH |
| 32353115 | Derived | Leung JH, Bayomy OF, Bonyhay I, Celli J, White J, Freeman R, Adler GK. ACTH Infusion Impairs Baroreflex Sensitivity-Implications for Cardiovascular Hypoglycemia-Associated Autonomic Failure. J Clin Endocrinol Metab. 2020 Jul 1;105(7):2345-53. doi: 10.1210/clinem/dgaa221. |
| NOT COMPLETED |
|
|
| NOT COMPLETED |
|
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
Subjects will receive normal saline infusion for two sessions of 2.5 hours each on day 2 of a three day admission to our research center.
Placebo: Subjects will receive placebo (normal saline infusion) for two sessions of 2.5 hours each on day 2 of a three day admission to our research center.
|
|
| Other Pre-specified | Pain (Quantitative Sensory Testing Using a Thermal Pain Testing Device) | Alterations in pain sensing will be evaluated pre and post with quantitative sensory testing using a thermal pain testing device, to evaluate the delayed effect of cosyntropin infusions. | Not Posted | 1 day after ACTH | Participants |
| Other Pre-specified | Hippocampal Memory (Paired Associative Learning Task) | Hippocampal memory will be evaluated pre and post with a paired associative learning task. Face Name Associative Memory Exam (FNAME) composite score on a scale from 0-36, with 36 being the best possible score. | Posted | Mean | Standard Deviation | score on a scale | 1 day after ACTH |
|
|
|
| 0 |
| 22 |
| 2 |
| 22 |
| EG001 | Cosyntropin | 0 | 21 | 0 | 21 | 0 | 21 |
| Subject had less blood drawn | General disorders | Subject with normal Hct at screen (37.8), had low Hct on admission (30.8 and 31.9). Due to general wellness the study proceeded; blood draws were reduced to primary endpoints/safety and only about 40cc of blood were drawn (reduced from about 165 cc). |
|
Not provided
Not provided
| D006728 |
| Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010908 | Pituitary Hormones, Anterior |
| D010907 | Pituitary Hormones |
| D009479 | Neuropeptides |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D009419 | Nerve Tissue Proteins |
| D011506 | Proteins |
| D000077324 | Crystalloid Solutions |
| D007552 | Isotonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |