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

Primary Purpose

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

Status

Recruiting

Phase

Phase 1

Locations

Spain

Study Type

Interventional

Intervention

Melatonin

Placebo

About this trial

This is an interventional treatment trial for Sclerosis, Multiple

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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).
Not having received any immunomodulatory, except for ocrelizumab in stable doses for at least 9 months before inclusion in this study, or immunosuppressive treatment (including cytostatic agents) during the 3 months prior to participation in the trial.
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.

Exclusion Criteria:

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.

Sites / Locations

Virgen Macarena HospitalRecruiting
Virgen del Rocio University HospitalRecruiting
Hospital Vithas Nisa SevillaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Melatonin

Control

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.

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.

Secondary Outcome Measures

Number of participants with treatment-related adverse events

To determine the incidence of adverse events and any abnormal laboratory values

Cerebral atrophy

Cerebral atrophy will be measured through magnetic resonance imaging

Fatigue

Fatigue will be assessed using the Modified Fatigue Impact Scale scale (MFIS), a modified form of the Fatigue Impact Scale (Fisk et al, 1994b) based on items derived from interviews with multiple sclerosis patients concerning how fatigue impacts their lives. The total score for the MFIS is the sum of the scores for the 21 items. Items on the MFIS can be aggregated into three subscales (physical, cognitive, and psychosocial), as well as into a total MFIS score. All items are scaled so that higher scores indicate a greater impact of fatigue on a person's activities.

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

Quality of life will be assessed using the Multiple Sclerosis International Quality of Life (MusiQoL) scale, a self-administered and multidimensional questionnaire designed to reflect the point of view held by patients with MS on how the disease affects their daily life. Questionnaire comprises 31 items describing nine dimensions: Activities of Daily Living, Psychological Well-Being, Symptoms, Relationships with Friends-Family-Healthcare System, Sentimental and Sexual Life, Coping and Rejection. Each item was scored on a six-point Likert scale: score of 1 (never ⁄not at all), 2 (rarely ⁄a little), 3 (sometimes ⁄somewhat), 4 (often ⁄ a lot), 5 (always ⁄ very much) and 6 (not applicable).

Sleep disorders

The assessment of sleep disorders will be conducted through the Pittsburgh Sleep Quality Index.

Spasticity

Spasticity will be analyzed using the Ashworth scale that tests resistance to passive movement about a joint with varying degrees of velocity. Scores range from 0-4, with 5 choices. A score of 1 indicates no resistance, and 5 indicates rigidity. 0 (0) - No increase in tone (1) - Slight increase in tone giving a catch when the limb was moved in flexion or extension (2) - More marked increase in tone but limb easily flexed (3) - Considerable increase in tone - passive movement difficult (4) - Limb rigid in flexion or extension.

Full Information

NCT ID

NCT03540485

First Posted

May 4, 2018

Last Updated

May 16, 2023

Sponsor

Fundación Pública Andaluza para la gestión de la Investigación en Sevilla

1. Study Identification

Unique Protocol Identification Number

NCT03540485

Brief Title

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

Official Title

Randomized, Double-blind, Placebo-controlled Clinical Trial to Evaluate the Safety and Efficacy of Melatonin Administration in Patients With Multiple Progressive Primary Sclerosis

Study Type

Interventional

2. Study Status

Record Verification Date

February 2023

Overall Recruitment Status

Recruiting

Study Start Date

November 29, 2019 (Actual)

Primary Completion Date

July 2024 (Anticipated)

Study Completion Date

December 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Fundación Pública Andaluza para la gestión de la Investigación en Sevilla

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

Detailed Description

Multiple sclerosis (MS), the most common inflammatory disease of the central nervous system in young adults, has a huge social and health interest, especially the primary progressive (PP-) course, in which the disability is very fast accumulated and currently there are no available treatments in Spain. PP-MS is characterized by neuro-inflammation and, especially, by neurodegeneration, with brain atrophy as key feature. It has been proposed that PP-MS therapies should combine anti-inflammatory and neuroprotective activities. The investigators have shown that melatonin, an immunomodulatory, antioxidant and neuroprotective compound, ameliorates the disease and modulates the pathogenic/protective immune responses in a MS animal model. Moreover, melatonin caused a long-term improvement of disability on a PP-MS patient. Thus, melatonin could be of interest in the therapy of PP-MS. So far, ocrelizumab, recently authorized by the European Medicines Agency and incorporated into the portfolio of the Spanish National Health System in December 2018, is the only therapy that has shown some therapeutic efficacy on the decrease in long-term disability. The purpose of this study is to determine the feasibility of using melatonin combined with ocrelizumab to treat PP-MS. Thus, the investigators propose a randomized, single-blind, placebo-controlled study on the safety and efficacy of melatonin combined with ocrelizumab on PP-MS patients. The investigators will assess the daily administration to patients treated with ocrelizumab for at least 9 months of one oral dose of melatonin containing 300mg during 24 months on patients safety and its effects over brain atrophy progression, Expanded Disability Status Scale scores, quality of life, MS symptoms, circadian impairment and levels of markers of central nervous system inflammation, axonal damage, Blood-brain barrier disruption and oxidative stress.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare Provider

Allocation

Randomized

Enrollment

50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Melatonin

Arm Type

Experimental

Arm Description

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

Arm Title

Control

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Melatonin

Intervention Description

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

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

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

Primary Outcome Measure Information:

Title

Rates of neurological impairment

Description

Time Frame

2 years

Title

Rates of disability

Description

Time Frame

2 years

Secondary Outcome Measure Information:

Title

Number of participants with treatment-related adverse events

Description

To determine the incidence of adverse events and any abnormal laboratory values

Time Frame

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

Title

Cerebral atrophy

Description

Cerebral atrophy will be measured through magnetic resonance imaging

Time Frame