EndometriosisPhase 2NCT00474851
The Effect of Hormonal Add-Back Therapy in Adolescents Treated With a GnRH Agonist for Endometriosis: A Randomized Trial
A Phase 2 study testing Norethindrone acetate + estrogens in people with Endometriosis, run by Boston Children's Hospital at 1 site in United States.
Trial summary
The purpose of this study is to determine whether a regimen of norethindrone acetate + placebo or norethindrone acetate + conjugated estrogens is superior in maintaining skeletal health and quality of life in adolescents treated with a GnRH agonist for endometriosis. Read more about this study
- Who is it for?
- Ages 13 to 22 years, women only
- Conditions the study is for
- Endometriosis
- What is being tested?
- Norethindrone acetate + estrogens
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 53 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2007to Jan 2015
- 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 13 to 22 years
- Women only
- No healthy volunteers
- Child, Adult
Who may be able to join
- Age 13-22 years, at least two years post-menarche
- Body mass index (BMI, kg/m2) between 18 -30 kg/m2
- Surgical diagnosis of endometriosis
- Clinical decision to treat with a GnRH agonist, leuprolide depot (Lupron Depot®; TAP Pharmaceuticals, Inc.) 11.25 mg intra-muscular every 3 months
Who cannot join
- Concomitant chronic diseases which affect bone health, such as cystic fibrosis, inflammatory bowel disease, renal disease, or diabetes mellitus
- Markedly impaired liver function or liver failure
- Personal history of thromboembolic event (such as deep venous thrombosis)
- Medication use known to affect bone metabolism:
- Glucocorticoid therapy (including inhaled steroids) or anticonvulsants used in the last 6 months
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Hospital Boston
Boston, Massachusetts, 02115
About this study
The purpose of this study is to determine whether a regimen of norethindrone acetate + placebo or norethindrone acetate + conjugated estrogens is superior in maintaining skeletal health and quality of life in adolescents treated with a GnRH agonist for endometriosis.
Read the detailed description
Endometriosis has become increasingly recognized as a chronic illness which begins during adolescence. Untreated endometriosis may lead to chronic pain and infertility. As recognition of the need for prompt therapy increases, so does the length of time patients will be exposed to treatments. As a result, there exists a pressing need to evaluate adjunctive measures that may limit the associated negative health consequences of treatment.
A gonadotropin-releasing hormone (GnRH) agonist is one medication utilized for patients who have failed other treatments. While GnRH-agonists are effective in relieving symptoms, their long-term use is problematic. GnRH agonists induce a low-estrogen state, causing deleterious effects on bone mineralization. These negative consequences are especially important for our pediatric patients. Adolescence is the critical period in a woman's life for bone acquisition and attainment of peak bone mass. Anything that interferes with this process puts patients at risk for lifelong low bone density and future fracture.
"Add-back" therapy appears to be a promising adjunct to treatment for prevention of this bone loss. Daily therapy with low-doses of hormones preserves bone density in adult patients, without altering the efficacy of the GnRH-agonist. However, no data exist on the effect of add-back therapy in adolescents.
The aim of the current study is to evaluate the safety and efficacy of two add-back regimens, norethindrone acetate + placebo or norethindrone acetate + conjugated estrogens, for the preservation of skeletal health and quality of life in adolescents with endometriosis treated with a GnRH-agonist.
- Conditions
- Endometriosis
- Being tested
- Norethindrone acetate + estrogens, norethindrone acetate + placebo
- Keywords
- Endometriosis, Adolescents, Bone density, GnRH Agonist, Add-back therapy
- Medical subject headings
- Endometriosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Norethindrone acetate + estrogensDrug
Also called Aygestin, Premarin
Norethindrone acetate 5 mg by mouth daily + Conjugated equine estrogens 0.625 mg by mouth daily
norethindrone acetate + placeboDrug
Also called Aygestin
norethindrone acetate 5 mg by mouth daily + Placebo capsule 1 pill by mouth daily
| Study group | Role | What they receive |
|---|---|---|
| Norethindrone acetate + estrogens | Experimental | Subjects randomized to the experimental arm received add-back therapy with norethindrone acetate 5 mg by mouth daily + conjugated equine estrogens 0.625 mg by mouth daily for the 12 months of study participation. Receives: Drug: Norethindrone acetate + estrogens |
| norethindrone acetate + placebo | Placebo comparator | Subjects randomized to the experimental arm received add-back therapy with norethindrone acetate 5 mg by mouth daily + a placebo capsule by mouth daily for the 12 months of study participation. Receives: Drug: norethindrone acetate + placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Bone Mineral Density
Adjusted mean change in total body areal bone mineral density (aBMD) over the 12 month trial
Measured: Baseline to 12 months
Secondary outcomes (1)
Total Body Bone Mineral Content (BMC)
Measured: Baseline to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 May 2007 (estimated)
- Study startAug 2007
- Primary completionOct 2013
- Study completionJan 2015
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.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for EndometriosisStudies of the same condition, open and under way.
- More trials run by Boston Children'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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 53 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boston Children's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Brigham and Women's Hospital
- Responsible party
- Principal investigator, Amy DiVasta, Boston Children's Hospital
- Investigators
- Amy D DiVasta, MD, MMSc, Principal investigator, Boston Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00474851
- Sponsor's protocol ID
- 07-01-0004
- Status last verified
- Mar 2015
- First submitted
- 15 May 2007
- Last updated
- 30 Mar 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Gallagher JS, DiVasta AD, Vitonis AF, Sarda V, Laufer MR, Missmer SA. The Impact of Endometriosis on Quality of Life in Adolescents. J Adolesc Health. 2018 Dec;63(6):766-772. doi: 10.1016/j.jadohealth.2018.06.027.
PubMed 30454733DiVasta AD, Feldman HA, Sadler Gallagher J, Stokes NA, Laufer MR, Hornstein MD, Gordon CM. Hormonal Add-Back Therapy for Females Treated With Gonadotropin-Releasing Hormone Agonist for Endometriosis: A Randomized Controlled Trial. Obstet Gynecol. 2015 Sep;126(3):617-627. doi: 10.1097/AOG.0000000000000964.
PubMed 26181088
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Hormonal Add-Back Therapy in Adolescents Treated With a GnRH Agonist for Endometriosis: A Randomized Trial
- ClinicalTrials.gov ID
- NCT00474851
- Acronym / sponsor ID
- 07-01-0004
- Conditions
- Endometriosis
- Keywords
- Endometriosis, Adolescents, Bone density, GnRH Agonist, Add-back therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 53 participants (actual)
- Lead sponsor
- Boston Children's HospitalUniversity, hospital or other
- Collaborators
- Brigham and Women's Hospital
- Study start
- Aug 2007
- Primary completion
- Oct 2013 (actual)
- Study completion
- Jan 2015 (actual)
- First posted
- 17 May 2007 (estimated)
- Results
- Posted 30 Mar 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether a regimen of norethindrone acetate + placebo or norethindrone acetate + conjugated estrogens is superior in maintaining skeletal health and quality of life in adolescents treated with a GnRH agonist for endometriosis.
Detailed description
Endometriosis has become increasingly recognized as a chronic illness which begins during adolescence. Untreated endometriosis may lead to chronic pain and infertility. As recognition of the need for prompt therapy increases, so does the length of time patients will be exposed to treatments. As a result, there exists a pressing need to evaluate adjunctive measures that may limit the associated negative health consequences of treatment.
A gonadotropin-releasing hormone (GnRH) agonist is one medication utilized for patients who have failed other treatments. While GnRH-agonists are effective in relieving symptoms, their long-term use is problematic. GnRH agonists induce a low-estrogen state, causing deleterious effects on bone mineralization. These negative consequences are especially important for our pediatric patients. Adolescence is the critical period in a woman's life for bone acquisition and attainment of peak bone mass. Anything that interferes with this process puts patients at risk for lifelong low bone density and future fracture.
"Add-back" therapy appears to be a promising adjunct to treatment for prevention of this bone loss. Daily therapy with low-doses of hormones preserves bone density in adult patients, without altering the efficacy of the GnRH-agonist. However, no data exist on the effect of add-back therapy in adolescents.
The aim of the current study is to evaluate the safety and efficacy of two add-back regimens, norethindrone acetate + placebo or norethindrone acetate + conjugated estrogens, for the preservation of skeletal health and quality of life in adolescents with endometriosis treated with a GnRH-agonist.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Norethindrone acetate + estrogens | Experimental | Drug: Norethindrone acetate + estrogensSubjects randomized to the experimental arm received add-back therapy with norethindrone acetate 5 mg by mouth daily + conjugated equine estrogens 0.625 mg by mouth daily for the 12 months of study participation. |
| norethindrone acetate + placebo | Placebo comparator | Drug: norethindrone acetate + placeboSubjects randomized to the experimental arm received add-back therapy with norethindrone acetate 5 mg by mouth daily + a placebo capsule by mouth daily for the 12 months of study participation. |
Who may qualify
- Ages
- 13 to 22 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- Age 13-22 years, at least two years post-menarche
- Body mass index (BMI, kg/m2) between 18 -30 kg/m2
- Surgical diagnosis of endometriosis
- Clinical decision to treat with a GnRH agonist, leuprolide depot (Lupron Depot®; TAP Pharmaceuticals, Inc.) 11.25 mg intra-muscular every 3 months
Key exclusion criteria (5 listed)
- Concomitant chronic diseases which affect bone health, such as cystic fibrosis, inflammatory bowel disease, renal disease, or diabetes mellitus
- Markedly impaired liver function or liver failure
- Personal history of thromboembolic event (such as deep venous thrombosis)
- Medication use known to affect bone metabolism:
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 + estrogensAlso: Aygestin, PremarinNorethindrone acetate 5 mg by mouth daily + Conjugated equine estrogens 0.625 mg by mouth daily | Drug | Norethindrone acetate + estrogens |
| norethindrone acetate + placeboAlso: Aygestinnorethindrone acetate 5 mg by mouth daily + Placebo capsule 1 pill by mouth daily | Drug | norethindrone acetate + placebo |
Primary outcome
Bone Mineral Density
Time frame: Baseline to 12 months
Adjusted mean change in total body areal bone mineral density (aBMD) over the 12 month trial
1 secondary outcome
Total Body Bone Mineral Content (BMC)
Time frame: Baseline to 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30454733Gallagher JS, DiVasta AD, Vitonis AF, Sarda V, Laufer MR, Missmer SA. The Impact of Endometriosis on Quality of Life in Adolescents. J Adolesc Health. 2018 Dec;63(6):766-772. doi: 10.1016/j.jadohealth.2018.06.027.
- Derived from this study: PubMed 26181088DiVasta AD, Feldman HA, Sadler Gallagher J, Stokes NA, Laufer MR, Hornstein MD, Gordon CM. Hormonal Add-Back Therapy for Females Treated With Gonadotropin-Releasing Hormone Agonist for Endometriosis: A Randomized Controlled Trial. Obstet Gynecol. 2015 Sep;126(3):617-627. doi: 10.1097/AOG.0000000000000964.
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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.
Amy D DiVasta, MD, MMSc principal investigator
Boston Children's Hospital
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 Norethindrone acetate + estrogens in people with Endometriosis, run by Boston Children's Hospital 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 4 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: finished, as of the sponsor's last update on 30 Mar 2015. 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. 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 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 Mar 2015). 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?
Bone Mineral Density (time frame: Baseline to 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00474851, which also lists 2 linked publications.
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 30 Mar 2015.