Sclerosis, MultiplePhase 1/2NCT03540485
Safety and Efficacy of Melatonin in Patients With Multiple Progressive Primary Sclerosis
A Phase 1/2 study testing Melatonin in people with Sclerosis, Multiple and Autoimmune Diseases of the Nervous System, run by Fundación Pública Andaluza para la gestión de la Investigación en Sevilla at 3 sites in Spain.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Sclerosis, Multiple, Autoimmune Diseases of the Nervous System, Nervous System Diseases
- What is being tested?
- Melatonin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 25 participants
- Where
- 3 sitesSpain
- Study dates
- 29 Nov 2019to 18 Feb 2026
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 11Show fewer
- 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.
Trial locations and contacts
3 sites in 1 country.
Spain3 sites
Virgen Macarena Hospital
Seville, Seville, 41009
Virgen del Rocio University Hospital
Seville, Seville, 41013
Hospital Vithas Nisa Sevilla
Seville, Seville, 41950
About this study
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
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.
Read the 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 100mg 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.
- Conditions
- Sclerosis, Multiple, Autoimmune Diseases of the Nervous System, Nervous System Diseases, Autoimmune Diseases
- Being tested
- Melatonin, Placebo
- Medical subject headings
- Multiple Sclerosis, Autoimmune Diseases of the Nervous System, Nervous System Diseases, Autoimmune Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MelatoninDrug
Daily administration of 100 mg of melatonin orally, for 24 months, single dose of melatonin between 10pm to 11pm
PlaceboOther
Daily administration of placebo orally, for 24 months between 10pm to 11pm
| Study group | Role | What they receive |
|---|---|---|
| Melatonin | Experimental | Daily administration of 100 mg of melatonin orally, for 24 months, single dose of melatonin between 10pm to 11pm Receives: Drug: Melatonin |
| Control | Placebo comparator | Daily administration of placebo orally, for 24 months between 10pm to 11pm Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 2 years
Secondary outcomes (6)
Number of participants with treatment-related adverse events
To determine the incidence of adverse events and any abnormal laboratory values
Measured: monthly from date of randomization until the end of the follow-up, assessed up to 24 months
Cerebral atrophy
Cerebral atrophy will be measured through magnetic resonance imaging
Measured: In every study visit, assessed up to 24 months
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.
Measured: In every study visit, assessed up to 24 months
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).
Measured: In every study visit, assessed up to 24 months
Sleep disorders
The assessment of sleep disorders will be conducted through the Pittsburgh Sleep Quality Index.
Measured: In every study visit, assessed up to 24 months
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.
Measured: In every study visit, assessed up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 May 2018
- Study start29 Nov 2019
- Primary completion18 Feb 2026
- Study completion18 Feb 2026
Why it stopped: Early termination due to operational feasibility reasons, resulting from a slow recruitment rate and logistical and financial difficulties that prevent reaching the planned sample size within the study schedule.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Sclerosis, MultipleStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Clara M Rosso Fernández, MD/PhD, Principal investigator, Clinical Research and Clinical Trials Unit (Virgen del Rocío University Hospital, Seville)Antonio Carrillo Vico, PhD, Study director, Institute of Biomedicine of Seville (IBiS)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03540485
- Sponsor's protocol ID
- MELATOMS-1
- Other IDs
- 2018-001779-18, 2018
- Status last verified
- Feb 2026
- First submitted
- 4 May 2018
- Last updated
- 20 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 41706381
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03540485
- Acronym / sponsor ID
- MELATOMS-1
- Conditions
- Sclerosis, Multiple, Autoimmune Diseases of the Nervous System, Nervous System Diseases, Autoimmune Diseases
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Early termination due to operational feasibility reasons, resulting from a slow recruitment rate and logistical and financial difficulties that prevent reaching the planned sample size within the study schedule.
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Fundación Pública Andaluza para la gestión de la Investigación en SevillaUniversity, hospital or other
- Study start
- 29 Nov 2019 (actual)
- Primary completion
- 18 Feb 2026 (actual)
- Study completion
- 18 Feb 2026 (actual)
- First posted
- 30 May 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 100mg 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Melatonin | Experimental | Drug: MelatoninDaily administration of 100 mg of melatonin orally, for 24 months, single dose of melatonin between 10pm to 11pm |
| Control | Placebo comparator | Other: PlaceboDaily administration of placebo orally, for 24 months between 10pm to 11pm |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (11 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MelatoninDaily administration of 100 mg of melatonin orally, for 24 months, single dose of melatonin between 10pm to 11pm | Drug | Melatonin |
| PlaceboDaily administration of placebo orally, for 24 months between 10pm to 11pm | Other | Control |
Primary outcome
Rates of neurological impairment
Time frame: 2 years
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
Time frame: 2 years
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.
6 secondary outcomes
Number of participants with treatment-related adverse events
Time frame: monthly from date of randomization until the end of the follow-up, assessed up to 24 months
Cerebral atrophy
Time frame: In every study visit, assessed up to 24 months
Fatigue
Time frame: In every study visit, assessed up to 24 months
Quality of life using the Multiple Sclerosis International Quality of Life scale
Time frame: In every study visit, assessed up to 24 months
Sleep disorders
Time frame: In every study visit, assessed up to 24 months
Spasticity
Time frame: In every study visit, assessed up to 24 months
Results and safety
The study was stopped early (reason given: Early termination due to operational feasibility reasons, resulting from a slow recruitment rate and logistical and financial difficulties that prevent reaching the planned sample size within the study schedule.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Feb 2026.
- Derived from this study: PubMed 41706381Bejarano 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clara M Rosso Fernández, MD/PhD principal investigator
Clinical Research and Clinical Trials Unit (Virgen del Rocío University Hospital, Seville)
Antonio Carrillo Vico, PhD study director
Institute of Biomedicine of Seville (IBiS)
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Melatonin in people with Sclerosis, Multiple and Autoimmune Diseases of the Nervous System, run by Fundación Pública Andaluza para la gestión de la Investigación en Sevilla at 3 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 20 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Early termination due to operational feasibility reasons, resulting from a slow recruitment rate and logistical and financial difficulties that prevent reaching the planned sample size within the study schedule.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rates of neurological impairment (time frame: 2 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03540485, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Feb 2026.