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Trial record 54 of 1726 for:    Recruiting, Not yet recruiting, Available Studies | Autoimmunity

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

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ClinicalTrials.gov Identifier: NCT03540485
Recruitment Status : Not yet recruiting
First Posted : May 30, 2018
Last Update Posted : May 24, 2019
Sponsor:
Information provided by (Responsible Party):
Fundación Pública Andaluza para la gestión de la Investigación en Sevilla

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

Condition or disease Intervention/treatment Phase
Sclerosis, Multiple Autoimmune Diseases of the Nervous System Nervous System Diseases Autoimmune Diseases Drug: Melatonin Other: Placebo Phase 1 Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Treatment
Official Title: Randomized, Single-blind, Placebo-controlled Clinical Trial to Evaluate the Safety and Efficacy of Melatonin Administration in Patients With Multiple Progressive Primary Sclerosis
Estimated Study Start Date : September 2019
Estimated Primary Completion Date : July 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Melatonin

Arm Intervention/treatment
Experimental: Melatonin
Daily administration of 300 mg of melatonin orally, for 24 months, single dose of melatonin between 10pm to 11pm
Drug: Melatonin
Daily administration of 300 mg of melatonin orally, for 24 months, single dose of melatonin between 10pm to 11pm

Placebo Comparator: Control
Daily administration of placebo orally, for 24 months between 10pm to 11pm
Other: Placebo
Daily administration of placebo orally, for 24 months between 10pm to 11pm




Primary Outcome Measures :
  1. 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.

  2. 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.


Secondary Outcome Measures :
  1. Number of participants with treatment-related adverse events [ Time Frame: montly from date of randomization until the end of the follow-up, assessed up to 24 months ]
    To determine the incidence of adverse events and any abnormal laboratory values

  2. Cerebral atrophy [ Time Frame: In every study visit, assessed up to 24 months ]
    Cerebral atrophy will be measured through magnetic resonance imaging

  3. Fatigue [ Time Frame: In every study visit, assessed up to 24 months ]
    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.

  4. Quality of life using the Multiple Sclerosis International Quality of Life scale [ Time Frame: In every study visit, assessed up to 24 months ]
    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).

  5. Sleep disorders [ Time Frame: In every study visit, assessed up to 24 months ]
    The assessment of sleep disorders will be conducted through the Pittsburgh Sleep Quality Index.

  6. Spasticity [ Time Frame: In every study visit, assessed up to 24 months ]

    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. (1) - Slight increase in tone giving a catch when the limb was moved in flexion or extension
    2. (2) - More marked increase in tone but limb easily flexed
    3. (3) - Considerable increase in tone - passive movement difficult
    4. (4) - Limb rigid in flexion or extension.

  7. Sleep-wake cycle [ Time Frame: In every study visit, assessed up to 24 months ]
    Ambulatory circadian monitoring will be evaluated using the Kronowise KW-6 (Kronohealth S.L) device for 7 days before the start and end of the trial.


Other Outcome Measures:
  1. Efficacy of neuroinflammation [ Time Frame: Day 0 and after 2 years ]
    Neuroinflammation marker CXCL13 will be measured through the human CXCL13 / BLC / BCA-1 Quantikine ELISA Kit (R & D Systems).

  2. Axonal damage [ Time Frame: Day 0 and after 2 years ]
    The levels of the axonal damage marker Neurofilament of the light chain (NfL) will be measured by the NF-light ELISA (UmanDiagnostics).

  3. Oxidative stress [ Time Frame: Day 0 and after 2 years ]
    Oxidative stress will be quantified through the analysis of the total antioxidant capacity (TAC) that will be evaluated through the OxiSelect Total Antioxidant Capacity (TAC) Assay Kit (CellBiolabs, Inc.).

  4. Impact on microbiota [ Time Frame: 2 years ]
    Comparison of biological alpha and beta diversity of the intestinal microbiota of both study groups (classical and optimized antibiotherapy). Calculation of alpha diversity (OTUs richness and Shannon diversity indexes observed, Faith's Phylogenetic Diversity and Evenness) and beta diversity (Jaccard distance, Bray- Curtis distance, Unweighted UniFra distance, used for comparing biological communities) indexes by QIIME 2 (microbiome bioinformatics platform).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Patients who come to the Multiple Sclerosis Unit of the Department of Neurology of the Virgen Macarena University Hospital (Seville, Spain) or Vithas Nisa Seville Hospital, 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 three 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 v.
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03540485


Contacts
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Contact: Clara M Rosso Fernández, MD/PhD 0034 955013414 claram.rosso.sspa@juntadeandalucia.es
Contact: Antonio Carrillo Vico, PhD 0034 955923106 vico@us.es

Locations
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Spain
Virgen Macarena Hospital Not yet recruiting
Seville, Spain, 41009
Contact: Juan L Ruiz Peña, MD, PhD         
Hospital Vithas Nisa Sevilla Not yet recruiting
Seville, Spain, 41950
Contact: Guillermo Izquierdo Ayuso, MD, PhD         
Sponsors and Collaborators
Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
Investigators
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Principal Investigator: Clara M Rosso Fernández, MD/PhD Clinical Research and Clinical Trials Unit (Virgen del Rocío University Hospital, Seville)
Study Director: Antonio Carrillo Vico, PhD Institute of Biomedicine of Seville (IBiS)

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Responsible Party: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
ClinicalTrials.gov Identifier: NCT03540485     History of Changes
Other Study ID Numbers: MELATOMS-1
2018-001779-18 ( EudraCT Number )
First Posted: May 30, 2018    Key Record Dates
Last Update Posted: May 24, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Autoimmune Diseases of the Nervous System
Autoimmune Diseases
Demyelinating Autoimmune Diseases, CNS
Multiple Sclerosis
Sclerosis
Nervous System Diseases
Pathologic Processes
Immune System Diseases
Demyelinating Diseases
Melatonin
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Central Nervous System Depressants