Low-Dose Naltrexone in Combination With Standard Treatment in Women With Endometriosis

Sponsor

Milton S. Hershey Medical Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT03970330

Collaborator

(none)

160

Enrollment

Location

Arms

39.5

Anticipated Duration (Months)

4.1

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Endometriosis	Drug: Naltrexone Drug: Norethindrone Acetate Drug: Placebo	Phase 3

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

Study Type:

Interventional

Anticipated Enrollment :

160 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Randomized, Double Blind, Placebo Controlled TrialRandomized, Double Blind, Placebo Controlled Trial

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jan 16, 2020

Anticipated Primary Completion Date :

May 1, 2023

Anticipated Study Completion Date :

May 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Low-Dose Naltrexone 12-week intervention period of 4.5 mg daily naltrexone in combination with standard treatment of 5-15 mg daily norethindrone acetate	Drug: Naltrexone 4.5mg daily dose, taken orally Other Names: REVIA Drug: Norethindrone Acetate 5 - 15mg daily dose, taken orally
Placebo Comparator: Placebo 12-week intervention period of daily placebo in combination with standard treatment of 5-15 mg daily norethindrone acetate	Drug: Norethindrone Acetate 5 - 15mg daily dose, taken orally Drug: Placebo daily placebo pill, taken orally

Arm

Intervention/Treatment

Experimental: Low-Dose Naltrexone

12-week intervention period of 4.5 mg daily naltrexone in combination with standard treatment of 5-15 mg daily norethindrone acetate

Drug: Naltrexone

4.5mg daily dose, taken orally

Other Names:

REVIA

Drug: Norethindrone Acetate

5 - 15mg daily dose, taken orally

Placebo Comparator: Placebo

12-week intervention period of daily placebo in combination with standard treatment of 5-15 mg daily norethindrone acetate

Drug: Norethindrone Acetate

5 - 15mg daily dose, taken orally

Drug: Placebo

daily placebo pill, taken orally

Outcome Measures

Primary Outcome Measures

Pain Score [12 weeks]
Pain will be 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 and normalized per participant to an average AUC score per week.

Secondary Outcome Measures

EHP-30 Score [Baseline, 4, 8, 12, and 16 weeks]
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) [4, 8, 12 and 16 weeks]
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) [4, 8, 12 and 16 weeks]
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) [4, 8, 12 and 16 weeks]
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 [12 weeks]
Total # of ibuprofen 200mg pills taken during the course of the study
Oxycodone use [12 weeks]
Total # of oxycodone 5mg pills taken during the course of the study

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 45 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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)