Effect of Melatonin on Reduction of Pelvic Pain

In two double blinded randomized controlled trials (RCT) we will study the effect of pain reduction of melatonin vs placebo in women with severe dysmenorrhea and women with endometriosis.The aim is to find an effective method for pelvic pain caused by dysmenorrhea and endometriosis.The primary outcome is reduction of pain in patients with dysmenorrhea and endometriosis respectively when treated with melatonin vs placebo. Secondary outcomes include the effect on daily life, quality of life and cognition. Sleep will also be assessed to evaluate its potential relation to quality of life and cognition.

Study Overview

• Status: Completed
• Conditions: Endometriosis; Dysmenorrhea
• Intervention / Treatment: Drug: Melatonin 10 mg; Drug: Placebo; Drug: Melatonin 20 mg

Detailed Description

Two substudies will be performed. Forty women with severe dysmenorrhea will be randomized to treatment with 10 mg melatonin daily or placebo during the menstruation for 2 menstrual cycles. Another 40 women with endometriosis will be randomized to treatment with 20 mg or placebo daily during 8 weeks. Participants will report drug intake, bleeding details (duration and amount) and pain as well as possible side effects. They will also perform a test for sleep quality and cognition before and after completion of the study.

See protocol for more details

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 2

Contacts and Locations

Study Locations

• Sweden
  • Stockholm, Sweden, 118 32
    • Sodersjukhuset

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Dysmenorrhea group

Inclusion Criteria:

• Regular menstrual cycles,
• Severe dysmenorrhea (NRS>6)
• Speaks and understands Swedish
• If other medication, those should be un-altered for the last 3 months

Exclusion Criteria:

• Smoker
• Prior or ongoing liver or kidney disease
• Endometriosis
• Pregnancy

Endometriosis group:

Criteria for inclusion:

• Endometriosis (endometriomas or diagnosis by laparoscopy)
• Moderate to severe pain (NRS >/= 4)
• Good general health
• Understands and speaks Swedish
• If any other treatment, unchanged regimen for the last 3 months
• Signed informed consent

Criteria for exclusion:

• Prior or ongoing disease in kidney or liver
• Use of opioid analgesics
• Smoker
• Pregnant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dysmenorrhea Melatonin 10 mg; In the dysmenorrhea group: 2 capsules with 5 mg melatonin will be given in the evening for seven days consecutively during menstruation for two mentrual cycles. Compared with placebo.	Drug: Melatonin 10 mg; Melatonin capsule; Other Names: N-acetyl-5-methoxy tryptamine; Drug: Placebo; Sugar pill manufactured to mimic Melatonin capsule; Other Names: Sugar pill
Experimental: Endometriosis Melatonin 20 mg; In the endometriosis group: 4 capsules with 5 mg melatonin will be given every evening during eight weeks. Compared with placebo.	Drug: Placebo; Sugar pill manufactured to mimic Melatonin capsule; Other Names: Sugar pill; Drug: Melatonin 20 mg; Melatonin capsule; Other Names: N-acetyl-5-methoxy tryptamine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain reduction	Self reported pain intensity daily, Numeric Rating Scale (NRS) 0-10 (0=no pain, 10 = worst possible pain)	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Use of analgesics	Self reported daily quantification of intake of analgesics reported online	12 weeks
Quality of sleep	Insomnia Severity index questionnaire will be administered during observational cycle and once during the second treatment cycle. 0 to 28 Points, 0-7 Points signifies no Clinical significant sleeping dificulties, 22-28 Points signifies Clinical insomnia)	12 weeks
Cognition	Dysmenorrhea group: Online test (CANTAB) performed on day 1-4 in the menstrual cycle in the observational cycle and in the second treatment cycle.	12 weeks
Catastrophic thinking	Endometriosis group: Pain Catastrophizing Scale questionnaire will be administered during observational cycle and once during the second treatment cycle. 0-52 Points, higher points indicate higher tendency to catastrophize.	12 weeks
General well being	Endometriosis group: Quality of life assessment with Endometriosis Health Profile (EHP-30) will be administered during observational cycle and once during the second treatment cycle. Score 0-100 Points, where 0 is best health status and 100 is worst health status.	12 weeks
Acceptance of Melatonin	Assessment at the end of study	12 weeks
Side effects of Melatonin	Online self reporting, daily	12 weeks

Collaborators and Investigators

• Sponsor: Karolinska Institutet

Publications and helpful links

General Publications

• Soderman L, Edlund M, Bottiger Y, Marions L. Adjuvant use of melatonin for pain management in dysmenorrhea - a randomized double-blinded, placebo-controlled trial. Eur J Clin Pharmacol. 2022 Feb;78(2):191-196. doi: 10.1007/s00228-021-03234-6. Epub 2021 Oct 20.

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2019
• Primary Completion (Actual): June 27, 2021
• Study Completion (Actual): June 30, 2021

Study Registration Dates

• First Submitted: November 14, 2018
• First Submitted That Met QC Criteria: December 19, 2018
• First Posted (Actual): December 20, 2018

Study Record Updates

• Last Update Posted (Actual): April 5, 2022
• Last Update Submitted That Met QC Criteria: April 4, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Pain; Neurologic Manifestations; Menstruation Disturbances; Endometriosis; Dysmenorrhea; Pelvic Pain; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Protective Agents; Antioxidants; Melatonin
• Other Study ID Numbers: Mel PP

Drug and device information, study documents

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