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The Effect of Hormonal Add-Back Therapy in Adolescents Treated With a GnRH Agonist for Endometriosis: A Randomized Trial

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ClinicalTrials.gov Identifier: NCT00474851
Recruitment Status : Completed
First Posted : May 17, 2007
Results First Posted : March 30, 2015
Last Update Posted : March 30, 2015
Sponsor:
Collaborator:
Brigham and Women's Hospital
Information provided by (Responsible Party):
Amy DiVasta, Boston Children’s Hospital

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Endometriosis
Interventions Drug: Norethindrone acetate + estrogens
Drug: norethindrone acetate + placebo
Enrollment 53
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Intervention Group Placebo Group
Hide Arm/Group Description

Conjugated equine estrogens: Conjugated estrogens 0.625 mg PO daily

Norethindrone acetate: Norethindrone acetate 5 mg PO daily

Placebo group

Placebo: Placebo capsule 1 pill PO daily

Norethindrone acetate: Norethindrone acetate 5 mg PO daily

Period Title: Overall Study
Started 26 27
Completed Baseline 25 26
Completed 18 16
Not Completed 8 11
Arm/Group Title Intervention Group Placebo Group Total
Hide Arm/Group Description

Conjugated equine estrogens: Conjugated estrogens 0.625 mg PO daily

Norethindrone acetate: Norethindrone acetate 5 mg PO daily

Placebo: Placebo capsule 1 pill PO daily

Norethindrone acetate: Norethindrone acetate 5 mg PO daily

Total of all reporting groups
Overall Number of Baseline Participants 25 26 51
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 25 participants 26 participants 51 participants
17.7  (1.4) 18.1  (1.9) 17.9  (1.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 25 participants 26 participants 51 participants
Female
25
 100.0%
26
 100.0%
51
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 25 participants 26 participants 51 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
Not Hispanic or Latino
25
 100.0%
26
 100.0%
51
 100.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 25 participants 26 participants 51 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
1
   4.0%
0
   0.0%
1
   2.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
   4.0%
0
   0.0%
1
   2.0%
White
23
  92.0%
26
 100.0%
49
  96.1%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 25 participants 26 participants 51 participants
25 26 51
1.Primary Outcome
Title Bone Mineral Density
Hide Description Adjusted mean change in total body areal bone mineral density (aBMD) over the 12 month trial
Time Frame Baseline to 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Intervention Group Placebo Group
Hide Arm/Group Description:

Conjugated equine estrogens: Conjugated estrogens 0.625 mg PO daily

Norethindrone acetate: Norethindrone acetate 5 mg PO daily

Placebo group

Placebo: Placebo capsule 1 pill PO daily

Norethindrone acetate: Norethindrone acetate 5 mg PO daily

Overall Number of Participants Analyzed 25 26
Mean (Standard Error)
Unit of Measure: g/cm^2
0.01  (0.006) -0.11  (0.006)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Intervention Group, Placebo Group
Comments

Analysis followed the intention-to-treat principle. The time course of each measurement from baseline to 3, 6, 9, and 12 months was compared between arms by repeated-measures analysis of variance (RM-ANOVA), with an autoregressive covariance model to account for visit-to-visit correlation within subjects.

The primary test of treatment efficacy was time × treatment interaction. Adjusted changes over time and differences between trial arms were constructed from parameters of the RMANOVA.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.10
Comments p (within group for subjects receiving norethindrone + conjugated estrogens)=0.05 p (within group for subjects receiving norethindrone + placebo)=0.65 p (between the two groups)=0.10
Method RMANOVA
Comments [Not Specified]
2.Secondary Outcome
Title Total Body Bone Mineral Content (BMC)
Hide Description [Not Specified]
Time Frame Baseline to 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Intervention Group Placebo Group
Hide Arm/Group Description:

Conjugated equine estrogens: Conjugated estrogens 0.625 mg PO daily

Norethindrone acetate: Norethindrone acetate 5 mg PO daily

Placebo: Placebo capsule 1 pill PO daily

Norethindrone acetate: Norethindrone acetate 5 mg PO daily

Overall Number of Participants Analyzed 25 26
Mean (Standard Error)
Unit of Measure: g
37  (10) 15  (11)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Intervention Group, Placebo Group
Comments

The time course of each measurement from baseline to 3, 6, 9, and 12 months was compared between arms by repeated-measures analysis of variance (RM-ANOVA), with an autoregressive covariance model to account for visit-to-visit correlation within subjects.

The primary test of treatment efficacy was time × treatment interaction. Adjusted changes over time and differences between trial arms were constructed from parameters of the RMANOVA.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.02
Comments p (within group for participants receiving norethindrone + estrogens)=0.0001 p (within group for participants receiving norethindrone + placebo)=0.31 p (between groups)=0.02
Method RMANOVA
Comments [Not Specified]
Time Frame Adverse events were evaluated every 3 months (at every research visit) for a total of 12 months (the duration of study participation).
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Intervention Group Placebo Group
Hide Arm/Group Description

Conjugated equine estrogens: Conjugated estrogens 0.625 mg PO daily

Norethindrone acetate: Norethindrone acetate 5 mg PO daily

Placebo group

Placebo: Placebo capsule 1 pill PO daily

Norethindrone acetate: Norethindrone acetate 5 mg PO daily

All-Cause Mortality
Intervention Group Placebo Group
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Intervention Group Placebo Group
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   8/25 (32.00%)      5/26 (19.23%)    
Gastrointestinal disorders     
Rectal bleeding *  1/25 (4.00%)  1 0/26 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Fracture * [1]  3/25 (12.00%)  3 0/26 (0.00%)  0
Psychiatric disorders     
Depression *  1/25 (4.00%)  1 5/26 (19.23%)  7
Reproductive system and breast disorders     
Hospitalization for pelvic/abdominal pain * [2]  3/25 (12.00%)  4 0/26 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
[1]
Bone fractures, secondary to fall or trauma. Non spontaneous, not low impact
[2]
All events determined to be likely due to flare of subject's underlying disease, endometriosis
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Intervention Group Placebo Group
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   15/25 (60.00%)      13/26 (50.00%)    
Musculoskeletal and connective tissue disorders     
Myalgias/arthralgias *  2/25 (8.00%)  2 2/26 (7.69%)  2
Psychiatric disorders     
Mood swings *  2/25 (8.00%)  2 1/26 (3.85%)  1
Reproductive system and breast disorders     
Pelvic pain * [1]  8/25 (32.00%)  11 8/26 (30.77%)  8
Vaginal bleeding *  3/25 (12.00%)  3 2/26 (7.69%)  2
*
Indicates events were collected by non-systematic assessment
[1]
Pain that did not require hospitalization or surgery
Sample of skeletally mature young women; Measurements of aBMD are two-dimensional and do not yield information regarding skeletal strength or microarchitecture
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Dr. Amy D. DiVasta
Organization: Boston Children's Hospital
Phone: 617-355-3792
Responsible Party: Amy DiVasta, Boston Children’s Hospital
ClinicalTrials.gov Identifier: NCT00474851     History of Changes
Other Study ID Numbers: 07-01-0004
First Submitted: May 15, 2007
First Posted: May 17, 2007
Results First Submitted: March 4, 2015
Results First Posted: March 30, 2015
Last Update Posted: March 30, 2015