Safety and Efficacy of Melatonin in Patients With Multiple Progressive Primary Sclerosis

NCT03540485 | Terminated Phase 1

• 2 other identifiers: MELATOMS-12018-001779-18
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 3

Brief Summary

Phase I / II randomized, double-blind, placebo-controlled clinical trial to evaluate the safety and efficacy of melatonin administration combined with ocrelizumab in patients with Progressive Multiple Primary Sclerosis.

Conditions

Sclerosis, Multiple; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Autoimmune Diseases

Outcome Measures

Primary Outcomes (2)

• Rates of neurological impairment

  Individualized rates of disease progression will be quantified using the rates of neurological impairment (Kurtzke Expanded Disability Status Scale). The scale provides a total score on a scale that ranges from 0 to 10. The first levels 1.0 to 4.5 refer to people with a high degree of ambulatory ability and the subsequent levels 5.0 to 9.5 refer to the loss of ambulatory ability.

  2 years

• Rates of disability

  Individualized rates of disease progression will be also quantified using the rates of disability (Multiple Sclerosis Functional Composite - MSFC scale).The MSFC measures are administered in person by a trained examiner. The MSFC can produce scores for each of the three individual measures (measure leg function/ambulation, arm/hand function, and cognitive function) as well as a composite score. Total administration time for all three measures should be approximately 20-30 minutes. Scores on component measures are converted to standard scores (z-scores), which are averaged to form a single MSFC score.

  2 years

Secondary Outcomes (6)

• Number of participants with treatment-related adverse events

  monthly from date of randomization until the end of the follow-up, assessed up to 24 months

• Cerebral atrophy

  In every study visit, assessed up to 24 months

• Fatigue

  In every study visit, assessed up to 24 months

• Quality of life using the Multiple Sclerosis International Quality of Life scale

  In every study visit, assessed up to 24 months

• Sleep disorders

  In every study visit, assessed up to 24 months

Other Outcomes (4)

• Efficacy of neuroinflammation

  Day 0 and after 2 years

• Axonal damage

  Day 0 and after 2 years

• Oxidative stress

  Day 0 and after 2 years

Study Arms (2)

Melatonin

EXPERIMENTAL

Daily administration of 100 mg of melatonin orally, for 24 months, single dose of melatonin between 10pm to 11pm

Drug: Melatonin

Control

PLACEBO COMPARATOR

Daily administration of placebo orally, for 24 months between 10pm to 11pm

Other: Placebo

Interventions

Melatonin DRUG

Daily administration of 100 mg of melatonin orally, for 24 months, single dose of melatonin between 10pm to 11pm

Melatonin

Placebo OTHER

Daily administration of placebo orally, for 24 months between 10pm to 11pm

Control

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients who come to the Multiple Sclerosis Unit of the Department of Neurology of the Virgen Macarena University Hospital (Seville) or Vithas Nisa Seville Hospital or Virgen del Rocío University Hospital (Seville), and who meet the following criteria:
• Have progressive primary multiple sclerosis according to McDonald's diagnostic criteria modified in 2010.
• Age between 18 and 65 years old.
• Neurological impairment measured with the Expanded Disability Status Scale (EDSS) scale between 2 and 7 (both included, without disability or only clinical symptoms up to ambulatory capacity with bilateral support).
• If there is a possibility of pregnancy (in women of childbearing age (15 to 44 years)) or paternity, accept the use of a highly effective method of birth control recommended by the Clinical Trial Facilitation Group (CTFG) during the treatment phase of the trial..
• Not having consumed melatonin or other dietary supplements (antioxidants or vitamins (tripling the recommended daily doses) during the month prior to participation in the trial.
• Ability to give informed consent and comply with the visits scheduled in the study.

You may not qualify if:

• Alternative diagnosis that explains both the neurological disability and the findings in nuclear magnetic resonance.
• Clinically significant medical problems that, in the opinion of the investigators, may cause tissue damage in the central nervous system or limit its repair, or that may expose the patient to unjustified risks or damages, or cause the patient not to complete the study.
• Clinical history of hypersensitivity reactions to melatonin.
• Pregnancy or lactation, or planning to become pregnant or patients of childbearing age not subject to birth control methods (recommended by the Clinical Trial Facilitation Group (CTFG)).
• Abnormal results in basal blood tests, defined as:
• Serum levels of alanine transaminase or aspartate transaminase greater than 1.5 times the upper limit of normal values.
• Total leukocyte count less than 3,000 / mm3.
• Platelet count less than 85,000 / mm3.
• Serum creatinine level greater than 2.0 mg / dL or glomerular filtration rate less than 30.
• Neurological deterioration measured with the Expanded Disability Status Scale scale of less than 2 or greater than 7.
• Be receiving any immunosuppressive therapy, except for ocrelizumab, including cytostatic agents.

Sponsors & Collaborators

• Fundación Pública Andaluza para la gestión de la Investigación en Sevilla: lead

Study Sites (3)

Virgen Macarena Hospital

Seville, Seville, 41009, Spain

Location

Virgen del Rocio University Hospital

Seville, Seville, 41013, Spain

Location

Hospital Vithas Nisa Sevilla

Seville, Seville, 41950, Spain

Location

Related Publications (1)

• Bejarano I, Jimenez-Jorge S, Lobo-Acosta MA, Alvarez-Lopez AI, Rosso-Fernandez CM, Lopez-Ruiz R, Eichau S, Ruiz-Pena JL, Geniz MA, Ampuero J, Ponce-Espana E, Merino-Bohorquez V, Camean M, Garcia-Sanchez MI, Izquierdo G, Guerrero JM, Romero-Gomez M, Lardone PJ, Carrillo-Vico A. Hepatic Safety of Adjunctive High-Dose Melatonin in Participants Receiving Ocrelizumab for Primary Progressive Multiple Sclerosis: Liver Toxicity Findings from a Phase I/II Randomised Clinical Trial (MELATOMS-1). CNS Drugs. 2026 Apr;40(4):579-596. doi: 10.1007/s40263-025-01261-w. Epub 2026 Feb 18.

  PMID: 41706381 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Autoimmune Diseases

Interventions

Melatonin

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Demyelinating Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Tryptamines; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Clara M Rosso Fernández, MD/PhD

  Clinical Research and Clinical Trials Unit (Virgen del Rocío University Hospital, Seville)

  PRINCIPAL INVESTIGATOR

• Antonio Carrillo Vico, PhD

  Institute of Biomedicine of Seville (IBiS)

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 4, 2018
• First Posted: May 30, 2018
• Study Start: November 29, 2019
• Primary Completion: February 18, 2026
• Study Completion: February 18, 2026
• Last Updated: February 20, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

ES (3)