Melatonin fOr CHronic bAck Pain (The MOCHA Trial)
NCT Number: NCT06476392
Acronym: MOCHA
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE3
Conditions: Back Pain Lower Back Chronic|Insomnia
Interventions: DRUG: Melatonin 10 MG|DRUG: Placebo
Sponsor: Odense University Hospital
Collaborators: University of Southern Denmark|University of Aarhus|Erasmus Medical Center|Odense Patient Data Explorative Network|T&W Engineering A/S
Sex: ALL
Age: ADULT
Enrollment: 220
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: QUADRUPLE (PARTICIPANT, CARE_PROVIDER, INVESTIGATOR, OUTCOMES_ASSESSOR)|Primary Purpose: TREATMENT
Start Date: 2024-09-01
Completion Date: 2026-11-01

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.

Primary Outcome Measures: 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 Outcome Measures: Insomnia severity, Insomnia will be assessed with the Insomnia Severity Index (ISI), which is a brief 7 item patient-reported instrument with a score ranging from 0-28 (0=best;28=worst), Baseline and after 6 weeks|Weekly pain intensity score trajectory, The trajectory of weekly numerical rating scale (NRS) pain intensity scores assessed on a 0-10 Numeric Rating Scale (NRS) (ranging from 'no pain to 'worst imaginable pain') from baseline to 6 weeks, Weekly from baseline to 6 weeks|30% pain intensity responders, Difference in number of patients with more than 30% improvement in pain intensity from baseline to 6 weeks, Change from baseline to 6 weeks|50% pain intensity responders, Difference in number of patients with more than 50% improvement in pain intensity from baseline to 6 weeks, Change from baseline to 6 weeks|Global Perceived Effect (GPE) for pain, Assessment of overall change in pain from baseline to 6 weeks. Participants will be asked at 6 weeks: 'How is your pain now compared to when you entered this study', with 5 response options (much worse, worse, almost the same/unchanged, improved, much improved), After 6 weeks|Physical and Mental Health, Physical and Mental Health will be assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS-10) Global Health questionnaire version 1.2. Difference in change in physical and mental health scores between treatment groups from baseline to 6 weeks. PROMIS-10 consist of 10 questions concerning different aspects of global health. The first 9 questions are score on a Likert scale with 5 response options, and the last question asks about pain using a 0-10 numeric rating scale, Baseline and after 6 weeks|Back pain related disability, Back pain related disability will be assessed using the Roland Morris Disability Questionnaire (RMQ). RMQ is a 23-item questionnaire (RMQ) developed to assess functional limitation and disability among patients with low back pain. The RMQ 23-item version will be used because 1) it has been cross-culturally validated in Danish (the original RMQ 24-item version has not), 2) the psychometric properties of the 23 vs 24 item RMQ have been shown to be similar. Each of the 23 items is yes/no (scored as 1 and 0 points respectively) with the scale ranging from 0 (no disability) to 23 (extremely severe disability)., Baseline and after 6 weeks
Other Outcome Measures: Time from sleep onset until final awakening (TST) from Ear EEG in subgroup of 60 patients, Difference in change in sleep metric between treatment groups (Melatonin \[n=30\] vs.placebo \[n=30\]) from baseline to 4 weeks. Sleep metrics will be derived from the EEG assessments as recommended by the American Academy of Sleep Medicine (AASM)., Baseline and week 4.|Sleep efficiency (SE) from Ear EEG in subgroup of 60 patients, Difference in change in sleep metric between treatment groups (Melatonin \[n=30\] vs.placebo \[n=30\]) from baseline to 4 weeks. Sleep metrics will be derived from the EEG assessments as recommended by the American Academy of Sleep Medicine (AASM). SE is the ratio of TST to time in bed / 100%, Baseline and week 4.|Sleep onset latency (SOL) from Ear EEG in subgroup of 60 patients, Difference in change in sleep metric between treatment groups (Melatonin \[n=30\] vs.placebo \[n=30\]) from baseline to 4 weeks. Sleep metrics will be derived from the EEG assessments as recommended by the American Academy of Sleep Medicine (AASM)., Baseline and week 4.|Wake after sleep onset (WASO) from Ear EEG in subgroup of 60 patients, Difference in change in sleep metric between treatment groups (Melatonin \[n=30\] vs.placebo \[n=30\]) from baseline to 4 weeks. Sleep metrics will be derived from the EEG assessments as recommended by the American Academy of Sleep Medicine (AASM)., Baseline and week 4.|REM sleep latency from Ear EEG in subgroup of 60 patients, Difference in change in sleep metric between treatment groups (Melatonin \[n=30\] vs.placebo \[n=30\]) from baseline to 4 weeks. Sleep metrics will be derived from the EEG assessments as recommended by the American Academy of Sleep Medicine (AASM)., Baseline and week 4.|Time from sleep onset until first epoch of REM stage sleep from Ear EEG, Difference in change in sleep metric between treatment groups (Melatonin \[n=30\] vs.placebo \[n=30\]) from baseline to 4 weeks. Sleep metrics will be derived from the EEG assessments as recommended by the American Academy of Sleep Medicine (AASM)., Baseline and week 4.|Amount of wake and stage N1, N2, N3, and R sleep as a percentage of SPT from Ear EEG, Difference in change in sleep metric between treatment groups (Melatonin \[n=30\] vs.placebo \[n=30\]) from baseline to 4 weeks. Sleep metrics will be derived from the EEG assessments as recommended by the American Academy of Sleep Medicine (AASM)., Baseline and week 4.|Number of awakenings within TST from Ear EEG, Difference in change in sleep metric between treatment groups (Melatonin \[n=30\] vs.placebo \[n=30\]) from baseline to 4 weeks. Sleep metrics will be derived from the EEG assessments as recommended by the American Academy of Sleep Medicine (AASM)., Baseline and week 4.|Arousal index which is number of arousals per hour from Ear EEG, Difference in change in sleep metric between treatment groups (Melatonin \[n=30\] vs.placebo \[n=30\]) from baseline to 4 weeks. Sleep metrics will be derived from the EEG assessments as recommended by the American Academy of Sleep Medicine (AASM)., Baseline and week 4.|Ease-of-use and Comfort with ear EEG, Three 0-10 questions are used: 1) How did you experience falling asleep with the ear EEG device, 2) How did you experience sleeping with the ear EEG device?, 3) How would you rate your experience of soreness or discomfort in your ears after sleeping with the device? A lower sum score is worse., Baseline and week 4.|Ear EEG adverse device effects, Any adverse device effect defined as an adverse effect related to the use of the ear EEG, Baseline and week 4.|Age, The age of the participant will be calculated using the date of randomisation and the date of birth., Baseline|Sex, The sex of the participant assigned at birth (male or female), Baseline|Height, Self-reported in centimeter, Baseline|Weight, Self-reported in kilograms, Baseline|Marital status, Self-reported marital status, Baseline|Level of education, The categories for level of education are compulsory education, upper secondary, bachelor degree, master degree, Phd degree, Baseline|Concomitant medication, Self-reported concomitant medication will be recorded in the eCRF by a trained nurse during the information visit., Baseline|Medical history and concomitant illnesses, Self-reported medical history and concomitant illnesses relevant to the investigation will be recorded in the eCRF. A clinically significant worsening of a concomitant illness will be reported as an AE, Baseline|Blood pressure, Diastolic and systolic, Baseline|Heart rate, Beats per min, Baseline|Serum levels of Alanintransaminase (ALAT), Blood test, Baseline|Serum levels of creatinine, Blood test, Baseline|Serum levels of Glomerular Filtration Rate (GFR), Blood test, Baseline|Choriogonadotropin (hCG), Urine test for pregnancy, Baseline and week 3|Pain sensitivity, Pressure pain threshold is assessed using a handheld algometer. Pressure pain thresholds will be assessed locally at the right erector spinae muscle (3 cm from the fourth lumbar spinous process) and at the left upper trapezius muscle (10 cm horizontally from the acromion in direct line with the seventh cervical spinous process)., Baseline and after 6 weeks.|Smoking status, Self-reported, Baseline|Alcohol consumption, Self-reported, Baseline|Physical activity level, Self-reported, Baseline|Work status, Self-reported, Baseline|Chronic pain, Chronic pain will be assessed using the Graded Chronic Pain Scale Revised (GCPS-R) questionnaire. The GCPS-R is a brief, freely available questionnaire that assesses frequency and severity of pain and its impact. The GCPS-R uses 5 items to categorize pain into no chronic pain, mild chronic pain, bothersome chronic pain, and high-impact chronic pain, Screening|Harms, In both groups the following will be reported:

Number of deaths Number of SAE Number of AE and categorized in mild and moderate, Week 3, week 6 and week 8