Melatonin for Knee Osteoarthritis Patients

NCT ID: NCT06012175

Last Updated: 2025-11-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 340 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-11-02
• Study Completion Date: 2025-09-24

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.

Conditions

Osteoarthritis, Knee

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Oral melatonin supplementation

Participants in the intervention arm will receive one 3 mg melatonin tablet every night before going to bed

Group Type: EXPERIMENTAL

Melatonin

Intervention Type: DIETARY_SUPPLEMENT

One 3 mg melatonin tablet every night before bedtime for 12 weeks

Placebo

The control group will receive an identical-looking inert placebo tablet every night before going to bed

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DIETARY_SUPPLEMENT

One placebo tablet, having an identical appearance to the melatonin tablet, every night before bedtime for 12 weeks

Interventions

Melatonin

One 3 mg melatonin tablet every night before bedtime for 12 weeks

Intervention Type: DIETARY_SUPPLEMENT

Placebo

One placebo tablet, having an identical appearance to the melatonin tablet, every night before bedtime for 12 weeks

Intervention Type: DIETARY_SUPPLEMENT

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.

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Peking University People's Hospital

OTHER

Sponsor Role: collaborator

West China Hospital

OTHER

Sponsor Role: collaborator

Massachusetts General Hospital

OTHER

Sponsor Role: collaborator

School of Medicine, University of Nottingham

UNKNOWN

Sponsor Role: collaborator

Xiangya Hospital of Central South University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Chao Zeng, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Xiangya Hospital of Central South University

Locations

Xiangya Hospital of Central South University

Changsha, Hunan, China

Countries

China

Other Identifiers

20230731

Identifier Type: -

Identifier Source: org_study_id