EndometriosisPhase 3NCT00458458
Treatment of Endometriosis With Norethindrone Acetate ( NA) VS. Gonadotropin- Releasing Hormone (GnRH) Agonist (Lupron Depot 11.25 mg)
A Phase 3 study testing Norethindrone Acetate (NA) and GnRH Agonist (Lupron Depot) in people with Endometriosis and Dysmenorrhea, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 1 site in United States.
Trial summary
(A) Major 1) to compare the effectiveness of norethindrone acetate (NA) with GnRH agonist (Lupron-Depot-3) in relieving symptoms of endometriosis, 2) to compare bone density in the two treated groups in order to demonstrate that NA does not affect bone density; (B) Minor: 1) To compare the lipid profiles of patients… Read more about this study
- Who is it for?
- Ages 18 to 55 years, women only
- Conditions the study is for
- Endometriosis, Dysmenorrhea, Dyspareunia
- What is being tested?
- Norethindrone Acetate (NA) and GnRH Agonist (Lupron Depot)
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 112 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2004to Dec 2012
- Phase
- Phase 3
- 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
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- The subject has voluntarily signed the Informed Consent form after having the contents fully explained, after all questions are answered and prior to undergoing any study-related procedures.
- The subject is a pre-menopausal female at least 18 years of age at the time of screening having regular periods (21-42 days intervals) with no menopausal symptoms.
- The subject has a diagnosis of endometriosis made via laparoscopy or laparotomy (operative report will be obtained) and still symptomatic and at least 3 months after surgery have a grade 2 and above according to Biberoglu's pain grade at screening visit (4 weeks prior initiation of treatment) or 4 out of 10 on a visual pain scale (visual analogue)
- Subject in good health, except for endometriosis, or has mild medical conditions that are stable and controlled. The subject has no clinically relevant hepatic, renal, cardiovascular, respiratory, endocrine, metabolic, psychiatric, neurologic (epilepsy), hematolytic (coagulopathy) and/or immunologic disease (on steroids) or disorder.
- A subject who has received any of the hormone therapies (GnRH agonist or danazol or progestin) must meet the minimum washout requirement to be eligible. (GnRH within the last 6 months and with steroids within the last month.) After hormonal therapy has stopped, the subject must have returned to normal for at least two menstrual cycles before baseline time.
- Serum pregnancy and urine qualitative pregnancy tests performed at screening and on baseline must be negative.
- Unless surgical sterile by bilateral tubal ligation or vasectomy of partner, the subject agrees to use a double-barrier method of contraception during the screening period, throughout the 24-week treatment period, such as: condom plus spermicide, diaphragm plus spermicide, sponge plus spermicide, abstinence is an acceptable form of birth control.
- Less than grade III overweight or BMI <40 kg/M2
Who cannot join
- Less than 3 months postpartum and post-lactation at the time of dosing.
- Abnormal laboratory findings considered clinically significant if more than twice the normal range. Abnormal tests will be repeated, and if still high as stated before, subject will be excluded.
- A previous history of significant adverse reactions to hormone, progestin or progesterone and GnRH agonist therapies.
- Abnormal Pap smear in the last 6 months. Subjects with ASCUS (atypical squamous cells of undetermined significance) and are negative for high-risk human papilloma virus (HPV) will be eligible. Subjects that have atypical endocervical cells, and atypical glandular cells are not eligible for this study.
- Subject has a bone density T score less or equal to 2.5, history of nontraumatic fracture, history of spinal surgery, history of fusion of lumbar region, history of severe scoliosis greater than 20 degrees.
Trial locations and contacts
1 site in 1 country.
United States1 site
SUNY Downstate Medical Center
Brooklyn, New York, 11203
About this study
(A) Major 1) to compare the effectiveness of norethindrone acetate (NA) with GnRH agonist (Lupron-Depot-3) in relieving symptoms of endometriosis, 2) to compare bone density in the two treated groups in order to demonstrate that NA does not affect bone density; (B) Minor: 1) To compare the lipid profiles of patients in the two groups to confirm the hypothesis that the effects of NA and GnRH agonists on lipid profiles are similar, 2) To determine whether quality of life, assessed by questionnaire, is better in patients assigned to NA than in patients assigned to GnRH, 3) To determine whether NA has fewer adverse effects than GnRH agonist.
Read the detailed description
Objectives: (A) Major 1) to compare the effectiveness of norethindrone acetate (NA) with GnRH agonist (Lupron-Depot-3) in relieving symptoms of endometriosis, 2) to compare bone density in the two treated groups in order to demonstrate that NA does not affect bone density; (B) Minor: 1) To compare the lipid profiles of patients in the two groups to confirm the hypothesis that the effects of NA and GnRH agonists on lipid profiles are similar, 2) To determine whether quality of life, assessed by questionnaire, is better in patients assigned to NA than in patients assigned to GnRH, 3) To determine whether NA has fewer adverse effects than GnRH agonist.
After signing an IRB approved consent from 112 women with symptomatic endometriosis, diagnosed surgically, will be treated with NA or Lupron-Depot-3 for 24 weeks. After 24 weeks both groups will be treated only with NA until 52 weeks. After that, both groups will be followed for an additional 52 weeks to assess any return of clinical symptoms and to determine whether laboratory tests of drug related changes return to pretreatment levels.
Treatment regimens are as follows: For the first 24 weeks, women in the NA group will be treated with 5 mg NA daily and a placebo injection every 12 weeks. In case of bleeding, the NA dose will be increased (max 15 mg) until bleeding stops, and then decreased by 2.5 mg every 4 weeks to a final dose of 7.5 mg which will be maintained for the remainder of the 24 weeks. For the first 24 weeks, women in the GnRH groups will receive Lupron-Depot-3 injections every 12 weeks plus placebo pills daily - bleeding will be treated with an increase in placebo pills to simulate treatment in the NA group. After 24 weeks, all women will be on identical regimens of 5 mg NA pills daily and no injections.
On the first treatment day, subjects will have the following tests/assessments: bone density with DEXA, scoring of endometriosis symptoms, quality of life questionnaire, general physical examination, lipid profile, estradiol (E2), N-telopeptide, and pregnancy test. All tests, except bone density and lipid profile, will be repeated at 12, 24, and 52 weeks of treatment. Bone density will be performed at 24 and 52 weeks and lipid profile will be performed at 12 and 52 weeks of treatment. In the follow-up period, physical examination, quality of life questionnaires, scoring of symptoms will be done at 3, 6, 9 and 12 months. Lipid profile, N-telopeptide and E2 will be performed at 3 and 12 months and bone density at 12 month follow-up.
The objectives stated above will be compared between the two groups at 12, 24, and 52 weeks of treatment and at 6-month intervals during the follow-up period.
- Conditions
- Endometriosis, Dysmenorrhea, Dyspareunia
- Being tested
- Norethindrone Acetate (NA), GnRH Agonist (Lupron Depot)
- Keywords
- Endometriosis, Dysmenorrhea, Pelvic Pain, Period Pain, Menstrual Cramps, Dyspareunia, Norethindrone Acetate, Lupron Depot, Bone Density, Lipid Profile
- Medical subject headings
- Endometriosis, Dysmenorrhea, Dyspareunia, Pelvic Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Norethindrone Acetate (NA)Drug
52 weeks of treatment with Norethindrone Acetate
GnRH Agonist (Lupron Depot)Drug
24 weeks of treatment with Lupron Depot then 28 weeks of treatment with Norethindrone Acetate
| Study group | Role | What they receive |
|---|---|---|
| NA alone | Active comparator | Norethindrone Acetate (NA) 5mg taken 1-3 tabs orally every night for duration of treatment Receives: Drug: Norethindrone Acetate (NA) |
| LD then NA | Active comparator | Lupron Depot(LD) given intramuscularly every 12 weeks for total of 24 weeks then switched to Norethindrone Acetate (NA) taken 1-3 tablets orally every night for remainder of treatment Receives: Drug: GnRH Agonist (Lupron Depot) |
What is being measured
The primary outcome is the main question the study is designed to answer.
To compare the effectiveness of norethindrone acetate (NA) with GnRH agonist (Lupron-Depot-3) in relieving symptoms of endometriosis
Measured: First 24 weeks of treatment
To compare effect of norethindrone acetate (NA) with GnRH agonist (Lupron-Depot-3)on bone density
Bone density with be compared in the two treated groups in order to demonstrate that NA does not affect bone density.
Measured: 52 weeks of treatment
Secondary outcomes (2)
To compare the effect of norethindrone acetate (NA) with GnRH agonist (Lupron-Depot-3)on lipid profiles
Lipid profiles of patients in the two groups will be collected to confirm the hypothesis that the effects of NA and GnRH agonists on lipid profiles are similar.
Measured: Treatment and follow-up
To determine the effect treatment has on quality of life
Quality of life will be assessed by questionnaire
Measured: Treatment and follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Apr 2007 (estimated)
- Study startAug 2004
- Primary completionDec 2012 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for EndometriosisStudies of the same condition, open and under way.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 112 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Sponsor type
- US National Institutes of Health
- Collaborators
- State University of New York - Downstate Medical Center, National Institutes of Health (NIH)
- Responsible party
- Principal investigator, Ozgul Muneyyirci-Delale, State University of New York - Downstate Medical Center
- Investigators
- Ozgul Muneyyirci-Delale, M.D., Principal investigator, State University of New York - Downstate Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00458458
- Sponsor's protocol ID
- 1R01HD043281
- Status last verified
- Oct 2012
- First submitted
- 9 Apr 2007
- Last updated
- 25 Oct 2012
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 25 Oct 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of Endometriosis With Norethindrone Acetate ( NA) VS. Gonadotropin- Releasing Hormone (GnRH) Agonist (Lupron Depot 11.25 mg)
- ClinicalTrials.gov ID
- NCT00458458
- Acronym / sponsor ID
- 1R01HD043281
- Conditions
- Endometriosis, Dysmenorrhea, Dyspareunia
- Keywords
- Endometriosis, Dysmenorrhea, Pelvic Pain, Period Pain, Menstrual Cramps, Dyspareunia, Norethindrone Acetate, Lupron Depot
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 112 participants (estimated)
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)US National Institutes of Health
- Collaborators
- State University of New York - Downstate Medical Center, National Institutes of Health (NIH)
- Study start
- Aug 2004
- Primary completion
- Dec 2012 (estimated)
- First posted
- 10 Apr 2007 (estimated)
- 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.
(A) Major 1) to compare the effectiveness of norethindrone acetate (NA) with GnRH agonist (Lupron-Depot-3) in relieving symptoms of endometriosis, 2) to compare bone density in the two treated groups in order to demonstrate that NA does not affect bone density; (B) Minor: 1) To compare the lipid profiles of patients in the two groups to confirm the hypothesis that the effects of NA and GnRH agonists on lipid profiles are similar, 2) To determine whether quality of life, assessed by questionnaire, is better in patients assigned to NA than in patients assigned to GnRH, 3) To determine whether NA has fewer adverse effects than GnRH agonist.
Detailed description
Objectives: (A) Major 1) to compare the effectiveness of norethindrone acetate (NA) with GnRH agonist (Lupron-Depot-3) in relieving symptoms of endometriosis, 2) to compare bone density in the two treated groups in order to demonstrate that NA does not affect bone density; (B) Minor: 1) To compare the lipid profiles of patients in the two groups to confirm the hypothesis that the effects of NA and GnRH agonists on lipid profiles are similar, 2) To determine whether quality of life, assessed by questionnaire, is better in patients assigned to NA than in patients assigned to GnRH, 3) To determine whether NA has fewer adverse effects than GnRH agonist.
After signing an IRB approved consent from 112 women with symptomatic endometriosis, diagnosed surgically, will be treated with NA or Lupron-Depot-3 for 24 weeks. After 24 weeks both groups will be treated only with NA until 52 weeks. After that, both groups will be followed for an additional 52 weeks to assess any return of clinical symptoms and to determine whether laboratory tests of drug related changes return to pretreatment levels.
Treatment regimens are as follows: For the first 24 weeks, women in the NA group will be treated with 5 mg NA daily and a placebo injection every 12 weeks. In case of bleeding, the NA dose will be increased (max 15 mg) until bleeding stops, and then decreased by 2.5 mg every 4 weeks to a final dose of 7.5 mg which will be maintained for the remainder of the 24 weeks. For the first 24 weeks, women in the GnRH groups will receive Lupron-Depot-3 injections every 12 weeks plus placebo pills daily - bleeding will be treated with an increase in placebo pills to simulate treatment in the NA group. After 24 weeks, all women will be on identical regimens of 5 mg NA pills daily and no injections.
On the first treatment day, subjects will have the following tests/assessments: bone density with DEXA, scoring of endometriosis symptoms, quality of life questionnaire, general physical examination, lipid profile, estradiol (E2), N-telopeptide, and pregnancy test. All tests, except bone density and lipid profile, will be repeated at 12, 24, and 52 weeks of treatment. Bone density will be performed at 24 and 52 weeks and lipid profile will be performed at 12 and 52 weeks of treatment. In the follow-up period, physical examination, quality of life questionnaires, scoring of symptoms will be done at 3, 6, 9 and 12 months. Lipid profile, N-telopeptide and E2 will be performed at 3 and 12 months and bone density at 12 month follow-up.
The objectives stated above will be compared between the two groups at 12, 24, and 52 weeks of treatment and at 6-month intervals during the follow-up period.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| NA alone | Active comparator | Drug: Norethindrone Acetate (NA)Norethindrone Acetate (NA) 5mg taken 1-3 tabs orally every night for duration of treatment |
| LD then NA | Active comparator | Drug: GnRH Agonist (Lupron Depot)Lupron Depot(LD) given intramuscularly every 12 weeks for total of 24 weeks then switched to Norethindrone Acetate (NA) taken 1-3 tablets orally every night for remainder of treatment |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- The subject has voluntarily signed the Informed Consent form after having the contents fully explained, after all questions are answered and prior to undergoing any study-related procedures.
- The subject is a pre-menopausal female at least 18 years of age at the time of screening having regular periods (21-42 days intervals) with no menopausal symptoms.
- The subject has a diagnosis of endometriosis made via laparoscopy or laparotomy (operative report will be obtained) and still symptomatic and at least 3 months after surgery have a grade 2 and above according to Biberoglu's pain grade at screening visit (4 weeks prior initiation of treatment) or 4 out of 10 on a visual pain scale (visual analogue)
- Subject in good health, except for endometriosis, or has mild medical conditions that are stable and controlled. The subject has no clinically relevant hepatic, renal, cardiovascular, respiratory, endocrine, metabolic, psychiatric, neurologic (epilepsy), hematolytic (coagulopathy) and/or immunologic disease (on steroids) or disorder.
- A subject who has received any of the hormone therapies (GnRH agonist or danazol or progestin) must meet the minimum washout requirement to be eligible. (GnRH within the last 6 months and with steroids within the last month.) After hormonal therapy has stopped, the subject must have returned to normal for at least two menstrual cycles before baseline time.
Key exclusion criteria (5 listed)
- Less than 3 months postpartum and post-lactation at the time of dosing.
- Abnormal laboratory findings considered clinically significant if more than twice the normal range. Abnormal tests will be repeated, and if still high as stated before, subject will be excluded.
- A previous history of significant adverse reactions to hormone, progestin or progesterone and GnRH agonist therapies.
- Abnormal Pap smear in the last 6 months. Subjects with ASCUS (atypical squamous cells of undetermined significance) and are negative for high-risk human papilloma virus (HPV) will be eligible. Subjects that have atypical endocervical cells, and atypical glandular cells are not eligible for this study.
- Subject has a bone density T score less or equal to 2.5, history of nontraumatic fracture, history of spinal surgery, history of fusion of lumbar region, history of severe scoliosis greater than 20 degrees.
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 |
|---|---|---|
| Norethindrone Acetate (NA)52 weeks of treatment with Norethindrone Acetate | Drug | NA alone |
| GnRH Agonist (Lupron Depot)24 weeks of treatment with Lupron Depot then 28 weeks of treatment with Norethindrone Acetate | Drug | LD then NA |
Primary outcome
To compare the effectiveness of norethindrone acetate (NA) with GnRH agonist (Lupron-Depot-3) in relieving symptoms of endometriosis
Time frame: First 24 weeks of treatment
To compare effect of norethindrone acetate (NA) with GnRH agonist (Lupron-Depot-3)on bone density
Time frame: 52 weeks of treatment
Bone density with be compared in the two treated groups in order to demonstrate that NA does not affect bone density.
2 secondary outcomes
To compare the effect of norethindrone acetate (NA) with GnRH agonist (Lupron-Depot-3)on lipid profiles
Time frame: Treatment and follow-up
To determine the effect treatment has on quality of life
Time frame: Treatment and follow-up
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Oct 2012.
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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.
Ozgul Muneyyirci-Delale, M.D. principal investigator
State University of New York - Downstate Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Norethindrone Acetate (NA) and GnRH Agonist (Lupron Depot) in people with Endometriosis and Dysmenorrhea, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) 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 8 inclusion and 5 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: status not confirmed, as of the sponsor's last update on 25 Oct 2012. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
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?
To compare the effectiveness of norethindrone acetate (NA) with GnRH agonist (Lupron-Depot-3) in relieving symptoms of endometriosis (time frame: First 24 weeks of treatment). The study lists 2 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 25 Oct 2012.