Melatonin for Chronic back pain

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Odense University Hospital

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

7 Nov 2024 → 13 Apr 2026

Decision date (initial)

2024-03-14

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

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.

Secondary objectives 5

1. 1) to compare the effect of drug Melatonin, relative to placebo, on pain-related disability
2. 2) to compare the effect of drug Melatonin, relative to placebo, on Global Perceived Effect (GPE)
3. 3) to compare the effect of drug Melatonin, relative to placebo, on insomnia
4. 4) to compare the effect of drug Melatonin, relative to placebo on health-related quality of life
5. 5) to compare the effect of drug Melatonin, relative to placebo, on pain sensitivity

Conditions and MedDRA coding

Chronic back pain

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Age 18 to 64 years
2. Back pain for 3 months or longer.
3. 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’)
4. 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’)
5. Average pain intensity of 4 on 0-10 Numeric Rating Scale [NRS] in the past 7 days (ranging from ‘no pain’ to ‘worst imaginable pain’).
6. 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 11

1. Known abuse of alcohol or other substances
2. 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
3. Self-selected non-user of e-boks
4. Opioid use (reported by participant)
5. Known malignancies within past 6 months (reported by participant)
6. Known fractures within past 4 months (reported by participant)
7. Known lumbar radiculopathy (reported by participant)
8. Known spinal stenosis (reported by participant)
9. Suicide and self-damage thoughts (reported by participant)
10. Inflammatory/autoimmune arthritis (reported by participant)
11. Patients with contraindications to Melatonin according to the Danish Medicines Agencys approved product information: 1) Moderate to severe kidney insufficiency (GFR < 30 mL/min), 2) Moderate to severe liver insufficiency (ALAT must not be elevated more than 3-fold over highest reference level) 3) Auto-immune diseases 4) Epilepsy 5) Warfarin use 6) Benzodiazipin use (including hypnotics) 7) Fluvoxamin use (Ciprofloxacin, Norfloxacin) 8) Calcium antagonist use (Verapamil, Nifedepin) 9) Pregnancy or pregnancy-wish or breastfeeding (a negative pregnancy test has to be available for all fertile female patients at baseline) 10) Intolerance to melatonin

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Average back pain intensity during the past 7 days. Difference in change between treatment groups (Melatonin vs. placebo) from baseline to 6 weeks. Average pain intensity during past 7 days will be assessed on a 0-10 Numeric Rating Scale (NRS) (ranging from ‘no pain to ‘worst imaginable pain’).

Secondary endpoints 8

1. Trajectory of weekly (at 0, 1, 2, 3, 4, 5 and 6 weeks) NRS back pain intensity scores (primary outcome) from baseline to 6 weeks.
2. Number of patients with more than 30% improvement in the primary outcome from baseline to 6 weeks (Number of responders are calculated for both the Melatonin and the placebo group).
3. Number of patients with more than 50% improvement in the primary outcome from baseline to 6 weeks (Number of responders are calculated for both the Melatonin and the placebo group).
4. Back pain related disability. Difference in change between treatment groups (Melatonin vs. placebo) from baseline to 6 weeks. Back pain related disability will be assessed using the Roland Morris Disability Questionnaire (RMQ).
5. Global Perceived Effect (GPE). Assessment of overall change in back pain from baseline to 6 weeks. Participants will be asked at 6 weeks: ‘How is your back pain now compared to when you entered this study’, with 5 response options (much worse, worse, almost the same/unchanged, improved, much improved).25
6. Physical and mental health will be assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS-10) Global Health questionnaire version 1.2.26 Difference in change in physical and mental health scores between treatment groups (Melatonin vs. placebo) 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 is asking about pain
7. Insomnia symptoms. Difference in change between treatment groups (Melatonin vs. placebo) from baseline to 6 weeks. 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), insomnia will be defined according to described cut-offs.
8. Pain sensitivity (i.e. pressure pain threshold). Difference in change between treatment groups (Melatonin vs. placebo) from baseline to 6 weeks. 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).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Odense University Hospital

Sponsor organisation

Odense University Hospital

Address

J B Winsloews Vej 4

City

Odense C

Postcode

5000

Country

Denmark

Scientific contact point

Organisation

Odense University Hospital

Contact name

Kübra Kilic

Public contact point

Organisation

Odense University Hospital

Contact name

Kübra Kilic

Third parties 1

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications