EndometriosisPhase 3NCT03970330
Low-Dose Naltrexone in Combination With Standard Treatment in Women With Endometriosis
A Phase 3 study testing Naltrexone and Norethindrone Acetate in people with Endometriosis, run by Milton S. Hershey Medical Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 45 years, women only
- Conditions the study is for
- Endometriosis
- What is being tested?
- Naltrexone and Norethindrone Acetate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Jan 2020to 21 Jun 2021
- Phase
- Phase 3
- 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 45 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 12Show fewer
- 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)
Trial locations and contacts
1 site in 1 country.
United States1 site
Penn State Hershey Medical Center
Hershey, Pennsylvania, 17033
About this study
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
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.
Read the 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).
- Conditions
- Endometriosis
- Being tested
- Naltrexone, Norethindrone Acetate, Placebo
- Keywords
- endometriosis, pelvic pain, opioid, narcotic
- Medical subject headings
- Endometriosis, Pelvic Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NaltrexoneDrug
Also called REVIA
4.5mg daily dose, taken orally
Norethindrone AcetateDrug
5 - 15mg daily dose, taken orally
PlaceboDrug
daily placebo pill, taken orally
| Study group | Role | What they receive |
|---|---|---|
| Low-Dose Naltrexone | Experimental | 12-week intervention period of 4.5 mg daily naltrexone in combination with standard treatment of 5-15 mg daily norethindrone acetate Receives: Drug: Naltrexone; Drug: Norethindrone Acetate |
| Placebo | Placebo comparator | 12-week intervention period of daily placebo in combination with standard treatment of 5-15 mg daily norethindrone acetate Receives: Drug: Norethindrone Acetate; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 weeks
Secondary outcomes (6)
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).
Measured: Baseline, 4, 8, 12, and 16 weeks
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).
Measured: 4, 8, 12 and 16 weeks
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).
Measured: 4, 8, 12 and 16 weeks
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).
Measured: 4, 8, 12 and 16 weeks
Ibuprofen Use
Average # of ibuprofen 200 mg pills per week during the study treatment period
Measured: 12 weeks
Oxycodone Use
Number of subjects who used oxycodone at any time during the study
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 May 2019
- Study start16 Jan 2020
- Primary completion21 Jun 2021
- Study completion21 Jun 2021
Why it stopped: Original PI left institution, lack of funding to continue
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 EndometriosisStudies of the same condition, open and under way.
- More trials run by Milton S. Hershey Medical CenterThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized, Double Blind, Placebo Controlled Trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Milton S. Hershey Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kristin Riley, MD, Milton S. Hershey Medical Center
- Investigators
- Kristin Riley, MD, Principal investigator, Milton S. Hershey Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03970330
- Sponsor's protocol ID
- Study00011187
- Status last verified
- Oct 2022
- First submitted
- 15 May 2019
- Last updated
- 3 Nov 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03970330
- Acronym / sponsor ID
- Study00011187
- Conditions
- Endometriosis
- Keywords
- endometriosis, pelvic pain, opioid, narcotic
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Original PI left institution, lack of funding to continue
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Milton S. Hershey Medical CenterUniversity, hospital or other
- Study start
- 16 Jan 2020 (actual)
- Primary completion
- 21 Jun 2021 (actual)
- Study completion
- 21 Jun 2021 (actual)
- First posted
- 31 May 2019 (actual)
- Results
- Posted 3 Nov 2022
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 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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized, Double Blind, Placebo Controlled Trial
| Arm | Type | Receives |
|---|---|---|
| Low-Dose Naltrexone | Experimental | Drug: Naltrexone, Drug: Norethindrone Acetate12-week intervention period of 4.5 mg daily naltrexone in combination with standard treatment of 5-15 mg daily norethindrone acetate |
| Placebo | Placebo comparator | Drug: Norethindrone Acetate, Drug: Placebo12-week intervention period of daily placebo in combination with standard treatment of 5-15 mg daily norethindrone acetate |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (12 listed)
- 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
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 |
|---|---|---|
| NaltrexoneAlso: REVIA4.5mg daily dose, taken orally | Drug | Low-Dose Naltrexone |
| Norethindrone Acetate5 - 15mg daily dose, taken orally | Drug | Low-Dose Naltrexone, Placebo |
| Placebodaily placebo pill, taken orally | Drug | Placebo |
Primary outcome
Pain Score Area Under the Curve (AUC)
Time frame: 12 weeks
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.
6 secondary outcomes
EHP-30 Score
Time frame: Baseline, 4, 8, 12, and 16 weeks
PGIC Score (Painful Periods)
Time frame: 4, 8, 12 and 16 weeks
PGIC Score (Nonmenstrual Pelvic Pain)
Time frame: 4, 8, 12 and 16 weeks
PGIC Score (Dyspareunia)
Time frame: 4, 8, 12 and 16 weeks
Ibuprofen Use
Time frame: 12 weeks
Oxycodone Use
Time frame: 12 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. 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.
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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.
Kristin Riley, MD principal investigator
Milton S. Hershey 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 Naltrexone and Norethindrone Acetate in people with Endometriosis, run by Milton S. Hershey Medical Center 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 6 inclusion and 12 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: stopped early, as of the sponsor's last update on 3 Nov 2022. 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 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?
Yes. Results are posted in the registry (first posted 3 Nov 2022). 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?
Pain Score Area Under the Curve (AUC) (time frame: 12 weeks). 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 3 Nov 2022.