Clinical trial NCT06476392: Melatonin for CHronic BAck Pain (The MOCHA Trial)
Official title: Melatonin for CHronic BAck Pain (The MOCHA Trial): a Randomized, Double Blind, Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Back Pain Lower Back Chronic
Insomnia
Lead sponsor: Odense University Hospital
Sponsor class: OTHER
Collaborators: name: University of Southern Denmark
name: T&W Engineering A/S
name: University of Aarhus
name: Region of Southern Denmark
name: Erasmus Medical Center
First posted: 2024-06-26
Enrollment: 220
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: The aim of this randomized double-blind placebo controlled clinical superiority trial is to investigate if daily treatment with Melatonin 10 mg once daily before bedtime for 6 weeks is superior compared with placebo in improving pain intensity assessed at 6 weeks after treatment initiation in patients with chronic back pain.

The primary objective is to compare the effect of the drug Melatonin, relative to placebo, on difference in change in pain intensity (i.e. average pain intensity past 7 days) measured on a 0-10 NRS scale, from baseline to 6 weeks in patients with chronic back pain.

Secondary objectives are to compare the effect of the drug Melatonin, relative to placebo, on 1) pain-related disability, 2) Global Perceived Effect (GPE), 3) insomnia severity, and 4) health-related quality of life. Furthermore, pain trajectory (0 to 6 weeks) and responder indices from baseline to 6 weeks will be compared between the treatment groups for the primary outcome.

Explorative objectives are to investigate changes in pain sensitivity (i.e. pressure pain threshold) and objective sleep metrics as well as effect-modification of presence/absence of comorbid insomnia.

Eligibility criteria: Inclusion Criteria:

To be eligible for the trial patients must fulfill all the following inclusion criteria:

* 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).

Exclusion Criteria:

Patients will be excluded based on any of the following exclusion criteria:

* 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
* Warfarin use
* Benzodiazipin use (including hypnotics)
* Fluvoxamin use (Ciprofloxacin, Norfloxacin)
* Calcium antagonist use (Verapamil, Nifedepin)
* Pregnancy or pregnancy-wish or breastfeeding (a negative pregnancy test has to be available for all fertile female patients at baseline)
* Intolerance to melatonin

For the EEG subgroup:

If the anatomy of the outer ear making it impossible to do ear EEG monitoring If there have a perforation of the tympanic membrane (eardrum) If they have an ear tube in the tympanic membrane If their ear piercings that are not compatible with ear EEG. If they use anticoagulants

Primary outcomes:
measure: Difference in change in average pain intensity during the last 7 days between groups
timeFrame: Difference in change from baseline to 6 weeks
Secondary outcomes:
measure: Insomnia severity
timeFrame: Baseline and after 6 weeks
measure: Weekly pain intensity score trajectory
timeFrame: Weekly from baseline to 6 weeks
measure: 30% pain intensity responders
timeFrame: Change from baseline to 6 weeks
measure: 50% pain intensity responders
timeFrame: Change from baseline to 6 weeks
measure: Global Perceived Effect (GPE) for pain
timeFrame: After 6 weeks
measure: Physical and Mental Health
timeFrame: Baseline and after 6 weeks
measure: Back pain related disability
timeFrame: Baseline and after 6 weeks
Other outcomes:
measure: Time from sleep onset until final awakening (TST) from Ear EEG in subgroup of 60 patients
timeFrame: Baseline and week 4.
measure: Sleep efficiency (SE) from Ear EEG in subgroup of 60 patients
timeFrame: Baseline and week 4.
measure: Sleep onset latency (SOL) from Ear EEG in subgroup of 60 patients
timeFrame: Baseline and week 4.
measure: Wake after sleep onset (WASO) from Ear EEG in subgroup of 60 patients
timeFrame: Baseline and week 4.
measure: REM sleep latency from Ear EEG in subgroup of 60 patients
timeFrame: Baseline and week 4.
measure: Time from sleep onset until first epoch of REM stage sleep from Ear EEG
timeFrame: Baseline and week 4.
measure: Amount of wake and stage N1, N2, N3, and R sleep as a percentage of SPT from Ear EEG
timeFrame: Baseline and week 4.
measure: Number of awakenings within TST from Ear EEG
timeFrame: Baseline and week 4.
measure: Arousal index which is number of arousals per hour from Ear EEG
timeFrame: Baseline and week 4.
measure: Ease-of-use and Comfort with ear EEG
timeFrame: Baseline and week 4.
measure: Ear EEG adverse device effects
timeFrame: Baseline and week 4.
measure: Age
timeFrame: Baseline
measure: Sex
timeFrame: Baseline
measure: Height
timeFrame: Baseline
measure: Weight
timeFrame: Baseline
measure: Marital status
timeFrame: Baseline
measure: Level of education
timeFrame: Baseline
measure: Concomitant medication
timeFrame: Baseline
measure: Medical history and concomitant illnesses
timeFrame: Baseline
measure: Blood pressure
timeFrame: Baseline
measure: Heart rate
timeFrame: Baseline
measure: Serum levels of Alanintransaminase (ALAT)
timeFrame: Baseline
measure: Serum levels of creatinine
timeFrame: Baseline
measure: Serum levels of Glomerular Filtration Rate (GFR)
timeFrame: Baseline
measure: Choriogonadotropin (hCG)
timeFrame: Baseline and week 3
measure: Pain sensitivity
timeFrame: Baseline and after 6 weeks.
measure: Smoking status
timeFrame: Baseline
measure: Alcohol consumption
timeFrame: Baseline
measure: Physical activity level
timeFrame: Baseline
measure: Work status
timeFrame: Baseline
measure: Chronic pain
timeFrame: Screening
measure: Harms
timeFrame: Week 3, week 6 and week 8
Locations:
city: Odense
country: Denmark
facility: Pain Center, University Hospital Odense
state: Funen
Study officials:
affiliation: University Hospital Odense
name: Karin Due Bruun, PhD
role: PRINCIPAL_INVESTIGATOR
References: