Melatonin fOr CHronic bAck Pain (The MOCHA Trial)

NCT06476392 | Completed Phase 3 DMC

• 1 other identifier: 2023-503530-41-00
• Study Type: interventional
• Target: 220
• Locations: 1 country
• Sites: 1

Brief Summary

According to the World Health Organization (WHO) Global Burden of Disease study, back pain is one of the conditions impacting disability the most worldwide.Pain medication use in patients with chronic back pain is substantial, but the efficacy of commonly used analgesics such as paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs), muscle relaxants and opioids compared with placebo are modest, with effects typically less than 10 points on a 0-100 pain scale. Importantly, these analgesics are not harmless due to gastrointestinal and cardiovascular side-effects (NSAIDs) and risk of dependency and addiction (opioids). This often leave general practitioners without good treatment options for many patients with chronic low back pain. More than half of patients with chronic back pain also have sleep problems (i.e. insomnia), which negatively affect daily function, general health and quality of life. Research suggest that insomnia has negative effects on pain processing, and although the relationship between pain and insomnia is bi-directional, insomnia is considered to be a stronger predictor of pain than pain for the development of insomnia. Melatonin is a widely available drug worldwide, and well known for its use in people with sleep disorders and jetlag. Melatonin is a naturally occurring hormone excreted by the pineal gland that is part of regulating the circadian rhythm (sleep-wake patterns). Unlike commonly used drugs to treat back pain, the safety profile of melatonin is favorable with no adverse events of major clinical significance reported in the treatment of sleep disorders. In recent years, some preliminary studies have showed a promising effect of Melatonin for treatments of pain. A meta-analysis reported an effect size of 0.65 (95%CI 0.34 to 0.96) of Melatonin (doses ranging between 3-10 mg before sleep) compared with placebo in reducing pain in patients with non-musculoskeletal chronic pain (e.g. migraine, irritable bowel syndrome, burning mouth syndrome), suggesting that Melatonin could potentially also be a valid treatment option for chronic musculoskeletal pain patients.

Conditions

Back Pain Lower Back Chronic; Insomnia

Outcome Measures

Primary Outcomes (1)

• Difference in change in average pain intensity during the last 7 days between groups

  Average pain intensity during last 7 days will be assessed on a 0-10 Numeric Rating Scale (NRS) (ranging from 'no pain to 'worst imaginable pain')

  Difference in change from baseline to 6 weeks

Secondary Outcomes (7)

• Insomnia severity

  Baseline and after 6 weeks

• Weekly pain intensity score trajectory

  Weekly from baseline to 6 weeks

• 30% pain intensity responders

  Change from baseline to 6 weeks

• 50% pain intensity responders

  Change from baseline to 6 weeks

• Global Perceived Effect (GPE) for pain

  After 6 weeks

Other Outcomes (32)

• Time from sleep onset until final awakening (TST) from Ear EEG in subgroup of 60 patients

  Baseline and week 4.

• Sleep efficiency (SE) from Ear EEG in subgroup of 60 patients

  Baseline and week 4.

• Sleep onset latency (SOL) from Ear EEG in subgroup of 60 patients

  Baseline and week 4.

Study Arms (2)

Melatonin

EXPERIMENTAL

2 Melatonin tablets (each 5 mg) once daily (egual 10 mg/day) in the evening, 30 min. before going to sleep for 6 weeks. If a participant experiences an adverse event deemed related to the study medication of grade 2 or higher according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 the dose will be reduced to 5 mg/day.

Drug: Melatonin 10 MG

Placebo

PLACEBO COMPARATOR

2 identical appearing placebo tablets once daily in the evening, 30 min. before going to sleep for 6 weeks. If a participant experiences an adverse event deemed related to the study medication of grade 2 or higher according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 the dose will be reduced to 1 tablet.

Drug: Placebo

Interventions

Melatonin 10 MG DRUG

2 Melatonin tablets (each 5 mg) once daily (egual 10 mg/day) in the evening, 30 min. before going to sleep for 6 weeks. If a participant experiences an adverse event deemed related to the study medication of grade 2 or higher according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 the dose will be reduced to 5 mg/day.

Also known as: Melatonin

Melatonin

Placebo DRUG

2 placebo tablets once daily in the evening, 30 min. before going to sleep for 6 weeks. If a participant experiences an adverse event deemed related to the study medication of grade 2 or higher according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 the dose will be reduced to 1 tablet.

Placebo

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18 to 64 years
• Understand and write Danish
• Back pain for 3 months or longer
• Back pain must be present on 'most days' or 'every day' within the past 3 months (will be checked by the question: 'In the past 3 months, how often did you have back pain? - response options: 'never'; 'some days'; 'most days'; 'every day')
• Back pain must limit life or work activities on 'some days', 'most days', or 'every day' within the past 3 months. (will be checked by the question: 'In the past 3 months, how often did your back pain limit your life or work activities? - response options: 'never'; 'some days'; 'most days'; 'every day')
• Average pain intensity of 4 or higher on 0-10 Numeric Rating Scale \[NRS\] in the past 7 days (ranging from 'no pain' to 'worst imaginable pain').
• All fertile women must use safe contraception (Spiral, birth control pills, contraceptive patch, contraceptive vaginal ring or gestagen injections) for 3 weeks before and 1 week after the trial. If the participants' normal lifestyle includes sexual abstinence, they do not have to use contraception. Instead, they can give an oral informed consent, that they will be sexually abstinent during the trial. A woman is considered non-fertile if she is sterilized, hysterectomized, bilateral oophorectomized or is postmenopausal. A woman is considered postmenopausal when vaginal bleeding has been absent for 1 year (reported by the participant).

You may not qualify if:

• Known abuse of alcohol or other substances
• Self-selected non-user of e-boks
• Opioid use (reported by participant)
• Known malignancies within past 6 months (reported by participant)
• Known fractures within past 4 months (reported by participant)
• Known lumbar radiculopathy (reported by participant)
• Known spinal stenosis (reported by participant)
• Severe psychiatric disorders and/or psychotic symptoms evaluated by the investigator (reported by participant)
• Suicide and self-damage thoughts (reported by participant)
• Inflammatory/autoimmune arthritis (reported by participant)
• Patients with contraindications to Melatonin according to the Danish Medicines Agencys approved product information:
• Moderate to severe kidney insufficiency (GFR \< 30 mL/min)
• Moderate to severe liver insufficiency (ALAT must not be elevated more than 3-fold over highest reference level)
• Auto-immune diseases
• Epilepsy

Sponsors & Collaborators

• Odense University Hospital: lead
• University of Southern Denmark: collaborator
• T&W Engineering A/S: collaborator
• University of Aarhus: collaborator
• Region of Southern Denmark: collaborator
• Erasmus Medical Center: collaborator

Study Sites (1)

Pain Center, University Hospital Odense

Odense, Funen, 5000, Denmark

Location

Related Publications (1)

• Kilic K, Vaegter HB, Bruun KD, Vach W, Hartvigsen J, Koes BW, Kidmose P, Sondergaard J, Thorlund JB. Melatonin for chronic back pain (the MOCHA trial): study protocol for a randomized, double-blind, placebo-controlled trial. Trials. 2025 Nov 17;26(1):513. doi: 10.1186/s13063-025-09206-w.

  PMID: 41250112 DERIVED

MeSH Terms

Conditions

Sleep Initiation and Maintenance Disorders

Interventions

Melatonin

Condition Hierarchy (Ancestors)

Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders

Intervention Hierarchy (Ancestors)

Tryptamines; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Karin Due Bruun, PhD

  University Hospital Odense

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participating patients, investigators, outcome assessors and statistical analysts are all blinded to treatment allocation. All patient reported data will be filled in by the patient via an online questionnaire using REDCap. An assessor blinded to study treatment will perform all protocol specific objective outcome assessments at baseline and 6 weeks follow-up. Unblinding will first take place after the primary analysis of the data has taken place. A data manager, otherwise, not involved in the study, will prepare the randomization list, using a computerized algorithm in REDCap.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 20, 2024
• First Posted: June 26, 2024
• Study Start: December 11, 2024
• Primary Completion: March 28, 2026
• Study Completion: April 13, 2026
• Last Updated: April 22, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)