Orthostatic Intolerance
Conditions
Brief summary
This study is designed to determine the causes of orthostatic intolerance which occurs more commonly in women than in men. Orthostatic tolerance is the ability to remain standing up right for long periods of time, or to avoid dizziness when moving to standing from a seated or lying position.
Detailed description
In this study we are interested in determining the impact of female reproductive hormones (estrogen and progesterone) on orthostatic tolerance (described above) so we administer these hormones to participants. We also test participants' orthostatic tolerance in our laboratory and use this information to place subjects into groups.
Interventions
Ganirelix acetate: .25 ml/day by subcutaneous injection
DRUG17β-Oestradiol
17 beta estradiol: 0.2 mg/day (patches)
DRUGProgesterone
progesterone, 200 mg day-1 oral
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Yale University
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 34 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy, English-speaking non-smoking women age 18- 34 with regular menses
Exclusion criteria
* Gynecologic: 1. current or past estrogen-dependent neoplasia, 2. unexplained vaginal bleeding, 3. history of uterine fibroids, 4. current pregnancy, 5. known or suspected breast or uterine cancer, 6. partial or complete hysterectomy * Cardiac: 1. myocardial infarction, ventricle tachycardia or fibrillation, 2. angina, 3. valvular disease, 4. congestive heart failure, orthopnea, paroxysmal nocturnal dyspnea, 5. current arrhythmias, 6. prosthetic valves * Pulmonary: 1. current cigarette smokers, or pipe or cigar smokers, 2. chronic obstructive pulmonary disease, 3. adult asthma, 4. dyspnea on exertion, 5. current bronchitis, pneumonia, or tuberculosis, 6. lung carcinoma, 7. pulmonary embolus, recent * Vascular: 1. claudication or history of peripheral vascular disease, 2. abdominal or thoracic aortic aneurysm, or repair of same, 3. cerebral aneurysm, vascular malformations, 4. hypertension, systolic or diastolic, or strong family history of hypertension * Gastrointestinal: 1. GI malignancy, 2. hepatitis, current, 3. splenomegaly from any cause, 4. Cholecystitis, 5. current diverticulosis or diverticulitis, inflammatory bowel disease, ulcerative colitis, Crohn's Disease, 6. previous gastrointestinal surgery * Infectious Disease: any intercurrent infection * Hematologic/Oncologic: 1. receiving chemotherapy or radiation therapy, 2. any metastatic malignancy, 3. anemia (hematocrit \< 35), 4. thrombocytopenia or thrombocytosis, 5. neutropenia, 6. hematologic malignancy, 7. bleeding dyscrasia * Neurologic: 1. history of cerebral vascular accident with any neurologic sequels, 2. uncontrolled seizures (e.g. more than 1 seizure/year), 3. transient ischemic attacks, 4. dementia, 5. neurologic conditions producing dyscoordination, peripheral neuropathy, or myopathy, 6. severe migraine headaches * Endocrine: 1. diabetes mellitus, 2. any untreated endocrinopathy * Renal: 1. chronic renal disease, 2. any history of renal disease or impairment, 3. current urinary tract infection * Musculoskeletal: 1. inflammatory arthritis history (e.g., rheumatoid, psoriatic, Reiters), 2. any history of pathologic fractures, including vertebral compression fractures * Pharmacologic: 1. any illegal drug use, 2. alcohol use greater than an average of 4 oz/day over 30 days, 3. coumadin or heparin use, 4. current systemic antifungal use
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Orthostatic Tolerance | 2 months | We used a measure called cumulative stress index to determine orthostatic tolerance, which is the amount of time at a level of negative pressure each subject can maintain before feeling as if she is going to pass out. This is calculated by multiplying the pressure in mm Hg by the time in min. |
| Baroreceptor Function | 2 months | This is a measure of how the body responds to changes in pressure induced by changes in position such as sitting, lying standing. The pressure changes are induced by gravity. The measurement described below to assess baroreceptor function is units of change in forearm vascular resistance for a given change in lower body negative pressure. This allows us to determine how good the body is at sending signals to the periphery to respond to postural changes. Baroreflex sensitivity is defined as the change in interbeat interval (IBI) in milliseconds per unit change in BP. For example, when the BP rises by 10 mmHg and IBI increases by 100 ms, BRS would be 100/10 = 10 ms/mmHg. |
| Skin Microvascular Responses | 2 months | Changes in blood flow in the small vessel in the skin are measured in response to sequential heat and drug stimulation. It is measured in volts, and then corrected for a maximum level and expressed as % max. This is measured with a Laser Doppler probes, which measures volts. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Women Estrogen and Progesterone
17 beta estradiol, progesterone, ganirelix acetate: Antagon (for ganirelix acetate)--0.25 ml per day, subcutaneous injection estradiol 0.2 mg/day (patches) per day progesterone 200 mg per day, pills
17 beta estradiol, progesterone, ganirelix acetate: 17 beta estradiol: 0.2 mg/day (patches) progesterone 200 mg/day ganirelix acetate 0.25 mg/day | 109 |
| Total | 109 |
Baseline characteristics
| Characteristic | Women |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 109 Participants |
| Age, Continuous | 22 years STANDARD_DEVIATION 1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 15 Participants |
| Race (NIH/OMB) Black or African American | 29 Participants |
| Race (NIH/OMB) More than one race | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 14 Participants |
| Race (NIH/OMB) White | 48 Participants |
| Region of Enrollment United States | 109 participants |
| Sex: Female, Male Female | 109 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 109 | 0 / 109 | 0 / 109 |
| serious Total, serious adverse events | 0 / 109 | 0 / 109 | 0 / 109 |
Outcome results
Primary
Baroreceptor Function
This is a measure of how the body responds to changes in pressure induced by changes in position such as sitting, lying standing. The pressure changes are induced by gravity. The measurement described below to assess baroreceptor function is units of change in forearm vascular resistance for a given change in lower body negative pressure. This allows us to determine how good the body is at sending signals to the periphery to respond to postural changes. Baroreflex sensitivity is defined as the change in interbeat interval (IBI) in milliseconds per unit change in BP. For example, when the BP rises by 10 mmHg and IBI increases by 100 ms, BRS would be 100/10 = 10 ms/mmHg.
Time frame: 2 months
Population: Women with low and high orthostatic tolerance
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Women With and Without Orthostatic Intolerance | Baroreceptor Function | 0.140 ms/mm Hg | Standard Error 0.034 |
| High Orthostatic Tolerant | Baroreceptor Function | 0.128 ms/mm Hg | Standard Error 0.044 |
Primary
Orthostatic Tolerance
We used a measure called cumulative stress index to determine orthostatic tolerance, which is the amount of time at a level of negative pressure each subject can maintain before feeling as if she is going to pass out. This is calculated by multiplying the pressure in mm Hg by the time in min.
Time frame: 2 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Women With and Without Orthostatic Intolerance | Orthostatic Tolerance | 634 mmHg*min | Standard Deviation 213 |
Primary
Skin Microvascular Responses
Changes in blood flow in the small vessel in the skin are measured in response to sequential heat and drug stimulation. It is measured in volts, and then corrected for a maximum level and expressed as % max. This is measured with a Laser Doppler probes, which measures volts.
Time frame: 2 months
Population: Women with and without orthostatic intolerance
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Women With and Without Orthostatic Intolerance | Skin Microvascular Responses | 4.02 Percent of max volts | Standard Error 0.39 |
| High Orthostatic Tolerant | Skin Microvascular Responses | 5.18 Percent of max volts | Standard Error 0.31 |
p-value: <0.05ANOVA