Clinical trial NCT06012175: Melatonin for Knee Osteoarthritis Patients
Official title: Efficacy and Safety of Melatonin for Pain Relief in Knee Osteoarthritis Patients: A Randomized, Double-Blind, Placebo-Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Osteoarthritis, Knee
Keywords: Osteoarthritis
Melatonin
Pain
Lead sponsor: Xiangya Hospital of Central South University
Sponsor class: OTHER
Collaborators: name: Peking University People's Hospital
name: West China Hospital
name: Massachusetts General Hospital
name: School of Medicine, University of Nottingham
First posted: 2023-08-25
Enrollment: 340
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: By recruiting knee osteoarthritis patients and treating them with melatonin, this study aims to determine the efficacy and safety of melatonin in alleviating pain in this patient population.

Detailed description: Knee osteoarthritis (KOA) is a major source of pain and disability among adults worldwide, but the treatment options for patients with painful KOA are inadequate. The current first-line oral drugs have only small to moderate benefits, and some may have serious adverse effects. Therefore, it is important to identify novel therapeutic medications with satisfactory efficacy and acceptable side-effect profiles for KOA.

Melatonin (N-acetyl-5-methoxytryptamine), an indolamine mainly secreted in the pineal gland, is generated from the amino acid tryptophan via derivatization reactions. There are numerous experimental and clinical data supporting the analgesic role of melatonin. In experimental studies, melatonin shows potent analgesic effects in a dose-dependent manner. In clinical studies, melatonin has been shown to have analgesic benefits in people with chronic painful conditions, such as fibromyalgia, irritable bowel syndrome, and migraine. In an animal OA study, the investigators found that melatonin reverses pain behaviors and synovial inflammation, and down-regulates pain sensitization-related neuromediators in the synovium. These findings suggest that melatonin may be potentially effective in treating OA-related pain. However, there is a paucity of high-quality clinical evidence from human studies.

The investigators propose to conduct a randomized, double-blind, placebo-controlled trial to examine the efficacy and safety of 12 weeks treatment with oral melatonin on pain and function in patients with KOA.

Eligibility criteria: Inclusion Criteria:

1. Age between 40 and 80 years.
2. Knee OA according to the American College of Rheumatology (ACR) clinical criteria.
3. Knee pain lasting 3 months or longer and a score of 7 or greater on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale (standardized to range from 0-20).
4. Kellgren-Lawrence (KL) grade 2 or 3.
5. Willing and able to provide written informed consent.

Exclusion Criteria:

1. Any use of NSAIDs or other analgesics in the past two weeks.
2. History of injections of corticosteroids in the past three months or hyaluronic acid in the past 6 months in the index knee.
3. History of arthroscopy or open surgery in the index knee in the past 12 months.
4. History of a knee replacement in the index knee or planning to receive such a procedure within 3 months.
5. History of a severe injury in the index knee.
6. Pain in the index knee caused by inflammatory, autoimmune, neoplastic diseases or other diseases.
7. Abnormal liver or kidney functions, as defined by alanine transaminase or aspartate aminotransferase \>two times the upper limit of normal, or blood urea nitrogen or serum creatinine \>two times the upper limit of normal.
8. Severe cardiopulmonary diseases.
9. Uncontrolled hypertension or diabetes mellitus.
10. Diagnosis of malignant tumors.
11. Pregnant or contemplating pregnancy or breastfeeding.
12. Any use of melatonin supplement before enrollment within 30 days.
13. Allergic to melatonin or its preparation.
14. Any use of anti-depressive/psychotropic drugs.

Primary outcomes:
measure: Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score.
timeFrame: Baseline, Week 12
Secondary outcomes:
measure: Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score.
timeFrame: Baseline, Weeks 2, 4, 6, 8 and 10
measure: Knee pain on a visual analogue scale (VAS).
timeFrame: Baseline, Weeks 2, 4, 6, 8, 10, and 12
measure: Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score.
timeFrame: Baseline, Weeks 2, 4, 6, 8, 10 and 12
measure: Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) stiffness score.
timeFrame: Baseline, Weeks 2, 4, 6, 8, 10 and 12
measure: Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function score.
timeFrame: Baseline, Weeks 2, 4, 6, 8, 10 and 12
measure: Patient global assessment of osteoarthritis (PGA-OA).
timeFrame: Baseline, Weeks 2, 4, 6, 8, 10 and 12
measure: SF-12 questionnaire.
timeFrame: Baseline, Weeks 2, 4, 6, 8, 10 and 12
measure: Hospital Anxiety and Depression Scale (HADS).
timeFrame: Baseline, Weeks 2, 4, 6, 8, 10 and 12
measure: Pittsburgh Sleep Quality Index (PSQI).
timeFrame: Baseline, Weeks 2, 4, 6, 8, 10 and 12
measure: Timed Up and Go Test (TUG).
timeFrame: Baseline, Weeks 4, 8, and 12
measure: 20-m Walk Test.
timeFrame: Baseline, Weeks 4, 8, and 12
measure: Chair-stand Test.
timeFrame: Baseline, Weeks 4, 8, and 12
measure: Ultrasound-assessed knee synovitis.
timeFrame: Baseline, Week 12
measure: Rescue medicine consumption.
timeFrame: Weeks 2, 4, 6, 8, 10 and 12
measure: C-reactive protein (CRP).
timeFrame: Baseline, Weeks 4, 8, and 12
measure: Microbiota diversity and composition.
timeFrame: Baseline, Weeks 4, 8, and 12
measure: Incidence of adverse events and serious adverse events.
timeFrame: Weeks 2, 4, 6, 8, 10 and 12
Other outcomes:
measure: Short Physical Performance Battery (SPPB) scores.
timeFrame: Baseline, Weeks 4, 8, and 12
measure: Grip strength.
timeFrame: Baseline, Week 4, 8, and 12
measure: Bone mineral density (BMD).
timeFrame: Baseline, Week 12
measure: DXA -based whole body muscle mass.
timeFrame: Baseline, Week 12
measure: DXA -based whole body fat mass.
timeFrame: Baseline, Week 12
Locations:
city: Changsha
country: China
facility: Xiangya Hospital of Central South University
state: Hunan
Study officials:
affiliation: Xiangya Hospital of Central South University
name: Chao Zeng, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: