Randomized, Double-blind, Placebo-controlled Clinical Trial to Evaluate the Safety and Efficacy of Melatonin Administration in Patients With Multiple Progressive Primary Sclerosis
概览
- 阶段
- 1 期
- 干预措施
- Melatonin
- 疾病 / 适应症
- Sclerosis, Multiple
- 发起方
- Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
- 入组人数
- 25
- 试验地点
- 3
- 主要终点
- Rates of disability
- 状态
- 终止
- 最后更新
- 2个月前
概览
简要总结
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.
详细描述
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.
研究者
入排标准
入选标准
- •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
- •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.
排除标准
- •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 / mm
- •Platelet count less than 85,000 / mm
- •Serum creatinine level greater than 2.0 mg / dL or glomerular filtration rate less than
- •Neurological deterioration measured with the Expanded Disability Status Scale scale of less than 2 or greater than
研究组 & 干预措施
Melatonin
Daily administration of 100 mg of melatonin orally, for 24 months, single dose of melatonin between 10pm to 11pm
干预措施: Melatonin
Control
Daily administration of placebo orally, for 24 months between 10pm to 11pm
干预措施: Placebo
结局指标
主要结局
Rates of disability
时间窗: 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.
Rates of neurological impairment
时间窗: 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.
次要结局
- Cerebral atrophy(In every study visit, assessed up to 24 months)
- Sleep disorders(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)
- 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)
- Fatigue(In every study visit, assessed up to 24 months)
- Spasticity(In every study visit, assessed up to 24 months)