Back to resultsLow-Dose Naltrexone in Combination With Standard Treatment in Women With Endometriosis
Primary Purpose
Endometriosis
Status
Terminated
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Naltrexone
Norethindrone Acetate
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Endometriosis focused on measuring endometriosis, pelvic pain, opioid, narcotic
Eligibility Criteria
Inclusion Criteria:
- Premenopausal female ages 18 to 45 years old on the day of signing informed consent.
- Must agree to use only study-specific analgesic medications during the study and is not known to be intolerant to them.
- Diagnosed with endometriosis and has had, within the last 10 years prior to signing the informed consent, surgical diagnosis with direct visualization and/or histopathologic confirmation of endometriosis.
- Is not expected to undergo gynecological surgery or other surgical procedures for treatment of endometriosis during the study period.
- Agrees to use contraception if not surgically sterile during the entire study.
- Patients using oral contraceptives, LARCs and/or GnRH agonists/antagonists for contraception and/or management of endometriosis, with a stable regimen, will be able to continue in the study, however, women using oral contraceptives and GnRH agonist/antagonists will be switched to Norethindrone acetate during the 1-2 week run-in period as prescribed by principle investigator.
Exclusion Criteria:
- Women that are pregnant, breastfeeding or trying to conceive.
- Patients with chronic daily narcotic use and any chronic pain or frequently reoccurring pain condition, other than endometriosis, that is treated with opioids or requires analgesics for more than 7 days per month.
- Patients with abnormal liver function tests (greater than 3x normal limit) in the past year or history of liver disease. Routine screening of liver function is not required.
- Non-English speaking or inability to read and understand English secondary, in part, to the need to read and report daily results in English.
- Undiagnosed vaginal bleeding
- Patients with history of opioid, illicit drug or alcohol abuse
- Patients currently taking thioridazine
- Patients with a history of suicidality
- Patients with current or history of unstable depression or other psychiatric disorder who, by PI judgement, are unstable or not well controlled
- Known, suspected or history of cancer of the breast
- Active deep vein thrombosis, pulmonary embolism or history of these conditions
- Active or recent arterial thromboembolic disease (e.g., stroke, myocardial infarction)
Sites / Locations
- Penn State Hershey Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Low-Dose Naltrexone
Placebo
Arm Description
12-week intervention period of 4.5 mg daily naltrexone in combination with standard treatment of 5-15 mg daily norethindrone acetate
12-week intervention period of daily placebo in combination with standard treatment of 5-15 mg daily norethindrone acetate
Outcomes
Primary Outcome Measures
Pain Score Area Under the Curve (AUC)
Pain is reported daily using the Visual Analog Scale, a 100mm horizontal line on which the patient's pain intensity is represented by a point between the extremities of 0 (no pain) and 100 (worst pain). The final outcome measure will be calculated as area under the curve from randomization through 12-weeks of intervention. AUC was calculated using the trapezoid rule. Calculated AUC per subject across this 12-week period can range from 0 - 8300.
Secondary Outcome Measures
EHP-30 Score
Quality of life measured by the validated Endometriosis Health Profile (EHP-30) questionnaire. Scores range from 0 (best health status) to 100 (worst health status).
PGIC Score (Painful Periods)
Patient's Global Impression of Change (PGIC) scale will be used to rate painful periods. This is a 7 point scale ranging from 1 (much worse) to 7 (much better).
PGIC Score (Nonmenstrual Pelvic Pain)
Patient's Global Impression of Change (PGIC) scale will be used to rate nonmenstrual pelvic pain. This is a 7 point scale ranging from 1 (much worse) to 7 (much better).
PGIC Score (Dyspareunia)
Patient's Global Impression of Change (PGIC) scale will be used to rate pelvic pain during sex. This is a 7 point scale ranging from 1 (much worse) to 7 (much better).
Ibuprofen Use
Average # of ibuprofen 200 mg pills per week during the study treatment period
Oxycodone Use
Number of subjects who used oxycodone at any time during the study
Full Information
NCT ID
NCT03970330
First Posted
May 15, 2019
Last Updated
October 8, 2022
Sponsor
Milton S. Hershey Medical Center
1. Study Identification
Unique Protocol Identification Number
NCT03970330
Brief Title
Low-Dose Naltrexone in Combination With Standard Treatment in Women With Endometriosis
Official Title
A Randomized Double-Blind Placebo-Controlled Trial to Assess the Effectiveness of Low-Dose Naltrexone in Combination With Standard Treatment in Women With Chronic Pelvic Pain Secondary to Endometriosis
Study Type
Interventional
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Terminated
Why Stopped
Original PI left institution, lack of funding to continue
Study Start Date
January 16, 2020 (Actual)
Primary Completion Date
June 21, 2021 (Actual)
Study Completion Date
June 21, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Milton S. Hershey Medical Center
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to determine if the addition of Low Dose Naltrexone to standard endometriosis treatments will improve patient reported endometriosis associated pain.
Detailed Description
The central hypothesis of the research study is that low dose naltrexone (LDN), in combination with hormonal suppression of endometriosis (standard of care), will lead to significant improvement of endometriosis-related pain.
The proposal seeks to:
determine if the addition of LDN to standard endometriosis treatments will improve patient- reported endometriosis associated pain using daily Visual Analogue Scale (VAS) scores and
measure the impact of treatment on quality of life as measured by validated questionnaires including the Endometriosis Health Profile-30 (EHP30) and the Patient's Global Impression of Change (PGIC).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Endometriosis
Keywords
endometriosis, pelvic pain, opioid, narcotic
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Randomized, Double Blind, Placebo Controlled Trial
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
9 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Low-Dose Naltrexone
Arm Type
Experimental
Arm Description
12-week intervention period of 4.5 mg daily naltrexone in combination with standard treatment of 5-15 mg daily norethindrone acetate
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
12-week intervention period of daily placebo in combination with standard treatment of 5-15 mg daily norethindrone acetate
Intervention Type
Drug
Intervention Name(s)
Naltrexone
Other Intervention Name(s)
REVIA
Intervention Description
4.5mg daily dose, taken orally
Intervention Type
Drug
Intervention Name(s)
Norethindrone Acetate
Intervention Description
5 - 15mg daily dose, taken orally
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
daily placebo pill, taken orally
Primary Outcome Measure Information:
Title
Pain Score Area Under the Curve (AUC)
Description
Pain is reported daily using the Visual Analog Scale, a 100mm horizontal line on which the patient's pain intensity is represented by a point between the extremities of 0 (no pain) and 100 (worst pain). The final outcome measure will be calculated as area under the curve from randomization through 12-weeks of intervention. AUC was calculated using the trapezoid rule. Calculated AUC per subject across this 12-week period can range from 0 - 8300.
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
EHP-30 Score
Description
Quality of life measured by the validated Endometriosis Health Profile (EHP-30) questionnaire. Scores range from 0 (best health status) to 100 (worst health status).
Time Frame
Baseline, 4, 8, 12, and 16 weeks
Title
PGIC Score (Painful Periods)
Description
Patient's Global Impression of Change (PGIC) scale will be used to rate painful periods. This is a 7 point scale ranging from 1 (much worse) to 7 (much better).
Time Frame
4, 8, 12 and 16 weeks
Title
PGIC Score (Nonmenstrual Pelvic Pain)
Description
Patient's Global Impression of Change (PGIC) scale will be used to rate nonmenstrual pelvic pain. This is a 7 point scale ranging from 1 (much worse) to 7 (much better).
Time Frame
4, 8, 12 and 16 weeks
Title
PGIC Score (Dyspareunia)
Description
Patient's Global Impression of Change (PGIC) scale will be used to rate pelvic pain during sex. This is a 7 point scale ranging from 1 (much worse) to 7 (much better).
Time Frame
4, 8, 12 and 16 weeks
Title
Ibuprofen Use
Description
Average # of ibuprofen 200 mg pills per week during the study treatment period
Time Frame
12 weeks
Title
Oxycodone Use
Description
Number of subjects who used oxycodone at any time during the study
Time Frame
12 weeks
10. Eligibility
Sex
Female
Gender Based
Yes
Gender Eligibility Description
Endometriosis is specifically associated to females.
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Premenopausal female ages 18 to 45 years old on the day of signing informed consent.
Must agree to use only study-specific analgesic medications during the study and is not known to be intolerant to them.
Diagnosed with endometriosis and has had, within the last 10 years prior to signing the informed consent, surgical diagnosis with direct visualization and/or histopathologic confirmation of endometriosis.
Is not expected to undergo gynecological surgery or other surgical procedures for treatment of endometriosis during the study period.
Agrees to use contraception if not surgically sterile during the entire study.
Patients using oral contraceptives, LARCs and/or GnRH agonists/antagonists for contraception and/or management of endometriosis, with a stable regimen, will be able to continue in the study, however, women using oral contraceptives and GnRH agonist/antagonists will be switched to Norethindrone acetate during the 1-2 week run-in period as prescribed by principle investigator.
Exclusion Criteria:
Women that are pregnant, breastfeeding or trying to conceive.
Patients with chronic daily narcotic use and any chronic pain or frequently reoccurring pain condition, other than endometriosis, that is treated with opioids or requires analgesics for more than 7 days per month.
Patients with abnormal liver function tests (greater than 3x normal limit) in the past year or history of liver disease. Routine screening of liver function is not required.
Non-English speaking or inability to read and understand English secondary, in part, to the need to read and report daily results in English.
Undiagnosed vaginal bleeding
Patients with history of opioid, illicit drug or alcohol abuse
Patients currently taking thioridazine
Patients with a history of suicidality
Patients with current or history of unstable depression or other psychiatric disorder who, by PI judgement, are unstable or not well controlled
Known, suspected or history of cancer of the breast
Active deep vein thrombosis, pulmonary embolism or history of these conditions
Active or recent arterial thromboembolic disease (e.g., stroke, myocardial infarction)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kristin Riley, MD
Organizational Affiliation
Milton S. Hershey Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Penn State Hershey Medical Center
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Participant data will be shared that underlie the results reported in this article, after deidentification. Documents that will be available are the study protocol, statistical analysis plan, informed consent. Analyses is to achieve the study aims in the approved proposal.
IPD Sharing Time Frame
Data will be available one year after publication according to PMCID journal guidelines.
IPD Sharing Access Criteria
Data will plan to be published in a peer-reviewed journal and /or posted at clinicaltrials.gov websites or other websites per request of the NIH. Materials will also be accessible through email contact of Primary Investigator.
Learn more about this trial
Low-Dose Naltrexone in Combination With Standard Treatment in Women With Endometriosis
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