Oxytocin for Hypermobile Ehlers-Danlos Syndrome (EDS-OXY)

Oxytocin Treatment for Chronic Pain in Hypermobile Ehlers-Danlos Syndrome

The purpose of this pilot study is to evaluate effect of IV oxytocin on chronic pain in patients with Hypermobile Ehlers Danlos syndrome.

Study Overview

• Status: Recruiting
• Conditions: Hypermobile Ehlers-Danlos Syndrome; Pain Assessment
• Intervention / Treatment: Other: Placebo; Drug: Oxytocin

Detailed Description

This will be a single-site study to evaluate the effect of IV oxytocin on chronic pain in female adult patients with hypermobile EDS.

Oxytocin secretion in the body is dynamic and can be affected by multiple factors including the menstrual period. In order to have minimum variation between tested individuals we conduct this study in females at the same stage of their menstrual cycles. Hypermobile EDS is more prevalent in females and the symptoms are usually more severe in females and more females come to medical attention. We are not aware of any difference in the risk from using oxytocin in females vs males.

All participating individuals are affected with hypermobile-EDS (hEDS) with chronic moderate to severe pain. Study will include two periods of treatment - one with placebo and one with oxytocin and a one month period will be held in between the two treatments. Participants will be blinded to the order of treatment. Each period of treatment will start 7-10 days after the beginning of the menstrual cycle and will include 6 days of daily subjective pain evaluation using pain-evaluation questionnaire ('preinfusion evaluation') followed by three consecutive daily infusions (placebo or oxytocin). Response to treatment will be evaluated by questionnaire during 6 days after each three infusion days (placebo or oxytocin) . Additional questionnaires for evaluation of anxiety and depression will be used as well. Patients will be asked to wear ACTIHEART device (measures heart rate, heart rate variation, and activity levels) 3 days prior to infusion, during the 3 days of infusion, and in the 3 days after the last infusion day. For each infusion period, participants will arrive to the study site for three daily consecutive visits, each will last for 3-4 hours. Response variables will be collected prior, during and after each infusion. Patients will fill out pain evaluation questionnaires pre and post infusion and some questionnaires during the days of infusion. Blood pressure and heart rate measurements will be taken prior, during and after the infusion. Blood samples for measurements of oxytocin levels and blood samples for future analysis will be collected in some of the infusion days (before and after the infusion).

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Alyssa Tran, BS; Phone Number: 8328224264; Email: alyssat@bcm.edu
• Study Contact Backup: Name: Keren Machol, MD, PhD; Phone Number: 8328224280; Email: Keren.Machol@bcm.edu

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • Baylor College of Medicine
      • Contact: Alyssa Tran, BS; Phone Number: 8328224264; Email: alyssat@bcm.edu
      • Contact: Keren Machol, MD, PhD; Phone Number: 832-822-4680; Email: Keren.Machol@bcm.edu
      • Principal Investigator: Brendan Lee, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 62 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1) Premenopausal Females, Age >18 years 2) Clinical diagnosis of hypermobile EDS according to the 2017 criteria for hEDS 3) Menstrual periods (range from 8 to 42 days) 4) Pain level greater that pain score of 4 out of 10 on a Numeric Rating Scale in at least two of the following locations: back, neck, shoulders, elbows, wrist, hand joints, hips, knees, ankles, on most days over the 3 months preceding enrollment. 5) On a stable regimen for pain control without any expected increase in dose of pain medications during the study period. 6) All participants should have a negative urine pregnancy test and agree to use an acceptable method of contraception (abstinence or barrier methods).

Exclusion Criteria:

1) Known allergy to OXT or preservatives in the medication 2) Pregnancy 3) Lactation 4) A confirmed clinical diagnosis of autoimmune disorders that lead to joint inflammation and joint pain such as SLE, RA, psoriatic arthritis, ankylosing spondylitis, scleroderma, and enteropathic arthritis 5) History of known cardiac arrhythmias (except for asymptomatic sinus tachycardia and sinus bradycardia) 6) Heart rate persistently greater than 110/min or less than 50 per minute 7) QTC of > 450 ms from EKG (electrocardiogram) test 8) Taking oral or other hormonal contraceptives 9) Individuals with a clinical condition which, in the view of the investigator compromises safety 10) Participating in another interventional study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo infusion: IV 0.9% NaCl, rate is 200ml over 40 minutes. Total of three infusions in three consecutive days (one per day)	Other: Placebo; IV, 200 ml 0.9%NaCl over 40 minutes. Total of three infusions in three consecutive days (one per day).
Active Comparator: Oxytocin; Treatment infusion: IV 1IU Oxytocin in 200ml of 0.9% NaCl, rate is 200ml over 40 minutes. Total of three infusions in three consecutive days (one per day)	Drug: Oxytocin; IV 1IU Oxytocin in 200 ml 0.9%NaCl over 40 minutes. Total of three infusions in three consecutive days (one per day).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in participant's subjective reported chronic pain	Change in the individual's subjective reported pain following treatment with oxytocin compared to treatment with placebo evaluated by using Brief Pain Inventory.	For each arm we will compare pain levels reported 6 days before infusion, 3 days of infusion, and 6 days post-infusion. This difference will be compared between the two treatment arms.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in heart rate patterns	Change in heart rate patterns following treatment with oxytocin compared to treatment with placebo for an objective functional outcome of pain as measured by Actiheart device.	For each arm we will compare changes in heart rate reported 3 days before infusion, 3 days of infusion, and 3 days post-infusion. This difference will be compared between the two treatment arms.
Change in activity level	Change in activity level following treatment with oxytocin compared to treatment with placebo for an objective functional outcome of pain as measured by Actiheart device.	For each arm we will compare changes in activity levels reported 3 days before infusion, 3 days of infusion, and 3 days post-infusion. This difference will be compared between the two treatment arms.
Changes in depression assessment	Change in reported signs of anxiety following treatment with oxytocin compared to treatment with placebo assessed by using the Hospital anxiety and depression scale.	For each arm we will compare depression levels reported 6 days before infusion, 3 days of infusion, and 6 days post-infusion. This difference will be compared between the two treatment arms.
Changes in anxiety assessment	Change in reported signs of anxiety following treatment with oxytocin compared to treatment with placebo assessed by using the State-Trait Anxiety Inventory.	For each arm we will compare anxiety levels reported 6 days before infusion, 3 days of infusion, and 6 days post-infusion. This difference will be compared between the two treatment arms.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in participant's pain levels assessed by numerical rating	Change in reported pain following treatment with oxytocin compared to treatment with placebo as assessed by using the Numerical pain rating scale.	For each arm we will compare pain levels reported 6 days before infusion, 3 days of infusion, and 6 days post-infusion. This difference will be compared between the two treatment arms.
Change in participant's pain levels by evaluating pain experience	Change in reported pain following treatment with oxytocin compared to treatment with placebo as assessed by using the McGill Pain Questionnaire.	For each arm we will compare pain levels reported 6 days before infusion, 3 days of infusion, and 6 days post-infusion. This difference will be compared between the two treatment arms.

Collaborators and Investigators

• Sponsor: Baylor College of Medicine
• Investigators: Principal Investigator: Brendan Lee, MD, PhD, Baylor College of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): May 13, 2022
• Primary Completion (Estimated): May 13, 2024
• Study Completion (Estimated): May 13, 2025

Study Registration Dates

• First Submitted: June 2, 2022
• First Submitted That Met QC Criteria: June 3, 2022
• First Posted (Actual): June 6, 2022

Study Record Updates

• Last Update Posted (Actual): July 28, 2023
• Last Update Submitted That Met QC Criteria: July 26, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: EDS, Oxytocin, Pain, Hypermobile Ehlers-Danlos Syndrome
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Disease; Congenital Abnormalities; Hematologic Diseases; Hemorrhagic Disorders; Genetic Diseases, Inborn; Connective Tissue Diseases; Hemostatic Disorders; Skin Diseases, Genetic; Skin Abnormalities; Collagen Diseases; Syndrome; Ehlers-Danlos Syndrome; Physiological Effects of Drugs; Reproductive Control Agents; Oxytocics; Oxytocin
• Other Study ID Numbers: H-45648

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No