Orthostatic IntolerancePhase 2NCT01153581
Sex Hormones and Orthostatic Tolerance
A Phase 2 study testing Ganirelix acetate, 17β-Oestradiol and Progesterone in people with Orthostatic Intolerance, run by Yale University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 34 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Orthostatic Intolerance
- What is being tested?
- Ganirelix acetate, 17β-Oestradiol and Progesterone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 109 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2006to May 2013
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 34 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy, English-speaking non-smoking women age 18- 34 with regular menses
Who cannot join
- Gynecologic:
- current or past estrogen-dependent neoplasia,
- unexplained vaginal bleeding,
- history of uterine fibroids,
- current pregnancy,
- known or suspected breast or uterine cancer,
Show all 65Show fewer
- partial or complete hysterectomy
- Cardiac:
- myocardial infarction, ventricle tachycardia or fibrillation,
- angina,
- valvular disease,
- congestive heart failure, orthopnea, paroxysmal nocturnal dyspnea,
- current arrhythmias,
- prosthetic valves
- Pulmonary:
- current cigarette smokers, or pipe or cigar smokers,
- chronic obstructive pulmonary disease,
- adult asthma,
- dyspnea on exertion,
- current bronchitis, pneumonia, or tuberculosis,
- lung carcinoma,
- pulmonary embolus, recent
- Vascular:
- claudication or history of peripheral vascular disease,
- abdominal or thoracic aortic aneurysm, or repair of same,
- cerebral aneurysm, vascular malformations,
- hypertension, systolic or diastolic, or strong family history of hypertension
- Gastrointestinal:
- GI malignancy,
- hepatitis, current,
- splenomegaly from any cause,
- Cholecystitis,
- current diverticulosis or diverticulitis, inflammatory bowel disease, ulcerative colitis, Crohn's Disease,
- previous gastrointestinal surgery
- Infectious Disease: any intercurrent infection
- Hematologic/Oncologic:
- receiving chemotherapy or radiation therapy,
- any metastatic malignancy,
- anemia (hematocrit < 35),
- thrombocytopenia or thrombocytosis,
- neutropenia,
- hematologic malignancy,
- bleeding dyscrasia
- Neurologic:
- history of cerebral vascular accident with any neurologic sequels,
- uncontrolled seizures (e.g. more than 1 seizure/year),
- transient ischemic attacks,
- dementia,
- neurologic conditions producing dyscoordination, peripheral neuropathy, or myopathy,
- severe migraine headaches
- Endocrine:
- diabetes mellitus,
- any untreated endocrinopathy
- Renal:
- chronic renal disease,
- any history of renal disease or impairment,
- current urinary tract infection
- Musculoskeletal:
- inflammatory arthritis history (e.g., rheumatoid, psoriatic, Reiters),
- any history of pathologic fractures, including vertebral compression fractures
- Pharmacologic:
- any illegal drug use,
- alcohol use greater than an average of 4 oz/day over 30 days,
- coumadin or heparin use,
- current systemic antifungal use
Trial locations and contacts
1 site in 1 country.
United States1 site
John B. Pierce Laboratory
New Haven, Connecticut, 06519
About this study
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.
Read the 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.
- Conditions
- Orthostatic Intolerance
- Being tested
- Ganirelix acetate, 17β-Oestradiol, Progesterone
- Medical subject headings
- Orthostatic Intolerance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ganirelix acetateDrug
Also called Antagon
Ganirelix acetate: .25 ml/day by subcutaneous injection
17β-OestradiolDrug
Also called 17 beta estradiol, estradiol
17 beta estradiol: 0.2 mg/day (patches)
ProgesteroneDrug
Also called P4, Prometrium
progesterone, 200 mg day-1 oral
| Study group | Role | What they receive |
|---|---|---|
| Ganirelix acetate | Experimental | Subjects were given 250 μg in 0.5ml normal saline for 16 days. (Organon, Roseland, NJ, USA) Receives: Drug: Ganirelix acetate |
| 17β-Oestradiol, E2 | Experimental | The same women added 17β-Oestradiol, E2; 0.2 mg day-1 patch (Vivelle; CIBA Pharmaceuticals, Summit, NJ) for days 4-16. Receives: Drug: 17β-Oestradiol |
| Progesterone | Experimental | The same women added progesterone (P4, 200 mg day-1 Prometrium, oral, Solvay Pharmaceuticals, Marietta, GA, USA) on days 13-16. Receives: Drug: Progesterone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 2 months
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.
Measured: 2 months
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.
Measured: 2 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jun 2010 (estimated)
- Study startFeb 2006
- Primary completionDec 2012
- Study completionMay 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Orthostatic IntoleranceStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe 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 2
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 109 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Sponsor
- Investigators
- Nina Stachenfeld, PhD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01153581
- Sponsor's protocol ID
- 0512000875a
- Other IDs
- 2R01HL071159-04
- Status last verified
- Nov 2018
- First submitted
- 28 Jun 2010
- Last updated
- 13 Dec 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Undecided: Our data are stored in locked files, and our spreadsheets and raw data are available should they be requested
Study at a glance
From the registry record, last updated by the sponsor on 13 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sex Hormones and Orthostatic Tolerance
- ClinicalTrials.gov ID
- NCT01153581
- Acronym / sponsor ID
- 0512000875a
- Conditions
- Orthostatic Intolerance
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 109 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Feb 2006
- Primary completion
- Dec 2012 (actual)
- Study completion
- May 2013 (actual)
- First posted
- 30 Jun 2010 (estimated)
- Results
- Posted 30 Jan 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Ganirelix acetate | Experimental | Drug: Ganirelix acetateSubjects were given 250 μg in 0.5ml normal saline for 16 days. (Organon, Roseland, NJ, USA) |
| 17β-Oestradiol, E2 | Experimental | Drug: 17β-OestradiolThe same women added 17β-Oestradiol, E2; 0.2 mg day-1 patch (Vivelle; CIBA Pharmaceuticals, Summit, NJ) for days 4-16. |
| Progesterone | Experimental | Drug: ProgesteroneThe same women added progesterone (P4, 200 mg day-1 Prometrium, oral, Solvay Pharmaceuticals, Marietta, GA, USA) on days 13-16. |
Who may qualify
- Ages
- 18 to 34 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Healthy, English-speaking non-smoking women age 18- 34 with regular menses
Key exclusion criteria (65 listed)
- Gynecologic:
- Cardiac:
- Pulmonary:
- Vascular:
- Gastrointestinal:
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 |
|---|---|---|
| Ganirelix acetateAlso: AntagonGanirelix acetate: .25 ml/day by subcutaneous injection | Drug | Ganirelix acetate |
| 17β-OestradiolAlso: 17 beta estradiol, estradiol17 beta estradiol: 0.2 mg/day (patches) | Drug | 17β-Oestradiol, E2 |
| ProgesteroneAlso: P4, Prometriumprogesterone, 200 mg day-1 oral | Drug | Progesterone |
Primary outcome
Orthostatic Tolerance
Time frame: 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
Time frame: 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
Time frame: 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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Dec 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided. Our data are stored in locked files, and our spreadsheets and raw data are available should they be requested
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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.
Nina Stachenfeld, PhD principal investigator
Yale University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ganirelix acetate, 17β-Oestradiol and Progesterone in people with Orthostatic Intolerance, run by Yale University at 1 site 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 1 inclusion and 65 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 13 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Jan 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Orthostatic Tolerance (time frame: 2 months). The study lists 3 primary outcomes in all. 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 13 Dec 2018.