E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
To evaluate the sleep quality in patients with Retinitis Pigmentosa |
Evaluar la calidad del sueño en pacientes con RP |
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E.1.1.1 | Medical condition in easily understood language |
To evaluate the sleep quality in patients with Retinitis Pigmentosa |
Evaluar la calidad del sueño en pacientes con RP |
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E.1.1.2 | Therapeutic area | Diseases [C] - Eye Diseases [C11] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To establish the therapeutic effect of melatonin, orally administered, on visual and sleep disturbances in adults patients affected by Retinitis Pigmentosa. |
Establecer la eficacia terapeútica de la melatonina, administrada por vía oral, sobre las alteraciones visuales y del sueño que sufren los pacientes adultos con Retinosis Pigmentaria. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the protective effect of melatonin, orally administered, in patients with Retinitis Pigmentosa, measuring the following parameters: 1.Sleep quality assesses by means of Sleep Quality questionnaires 2.Rest-activity cycles monitored by actigraph recording. 3.Oxidative stress quantified by measurement of malondialdehyde and 4- hydroxyalkenals, protein carbonyl, nitrites, total antioxidant status, melatonin, and activities of catalase, glutathione reductase, glutathione peroxidase, and superoxide dismutase. 4.Visual function assessed by Visual function best corrected visual acuity ETDRS scale or low vision ones, Funduscopy evaluation, Macular and Retinal Nerve Fiber Layer measured by Spectral Domain Optical Coherence Tomography, Electoretinogram (ERG) and automated perimetry. 5.Life quality evaluated by the National Eye Institute Visual Functioning Questionnaire.25 (NEI VFQ-25) |
Evaluar el efecto protector de la melatonina, administrada por vía oral a los pacientes con Retinosis Pigmentaria, mediante los siguientes parámetros: 1.Calidad del sueño, valorada mediante los cuestionarios de calidad de sueño. 2.Ritmo sueño-vigilia, cuantificado mediante el registro actimétrico. 3.Estado oxidativo, cuantificado mediante la determinación de cuantificación de malonildialdehido y 4-hidroxialquenales, restos carbonilo de las proteínas, nitritos, melatonina, actividad total antioxidante y de la superóxido dismutasa, catalasa, glutation reductasa y glutation peroxidasa. 4.Función visual, valorada mediante test de AV con optotipos ETDRS u optotipos de baja visión, evaluación del Fondo de Ojo mediante fundoscopia y OCT macular, ERG y perimetría automatizada. 5.Calidad de vida del enfermo, valorada mediante los cuestionarios de calidad de vida del enfermo. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
a)Patients from de Ophthalmology Department b)Being 18 years old or older c)Diagnosed with Retinitis Pigmentosa d)Visual acuity equal or less than 20/200 e) In case of any other pathologies, treated with the standard treatment following the international directions and the protocols established by the Ophthalmic Unit f)Signed informed consent |
a)Paciente del Servicio de Oftalmología b)Edad igual o superior a 18 años c)Cumplimiento de los criterios diagnósticos de Retinosis Pigmentaria d)Con Agudeza Visual (AV) igual o inferior a 20/200 e)Recibir el tratamiento estándar, en caso de existir otras patologías, de acuerdo con las directrices universalmente aceptadas y con los protocolos del Servicio de Oftalmología f)Consentimiento informado firmado |
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E.4 | Principal exclusion criteria |
a) No informed consent b) Absence of other ophthalmological treatments if needed c) Patients affected by atypical forms of Retinitis Pigmentosa as sector or paravenous forms, Bardet Biedl or Refsum syndromes, or Retinitis punctata albescens. d) Patients with other systemic pathologies or deafness (excluding Usher syndrome) e) Pregnancy (or a likelihood of becoming pregnant) or lactation. f) Patients with other retinal diseases |
a)Ausencia de consentimiento informado b)Ausencia de tratamiento oftalmológico por patologías concomitantes c)Paciente con formas ati?picas de Retinosis Pigmentaria (como formas en sector, paravenosas, sindrome de Bardet-Bield y de Refsum y Retinitis Puntata Albecens). d)Paciente con otras patologi?as siste?micas o sordera (exceptuando Síndrome de Usher). e)Embarazadas o con posibilidad de estarlo o en lactancia f)Paciente que asocia otras patologi?as retinianas intercurrentes. |
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E.5 End points |
E.5.1 | Primary end point(s) |
-Sleep quality assessed by means of the Pittsburg Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and the Horne and Ostberg Morningness/Eveningness Questionnaire. -Life quality evaluated by the National Eye Institute Visual Functioning Questionnaire.25 (NEI VFQ-25) -Rest-activity cycles monitored by an actimeter that the patient wears like a wristwatch, recording the amount of movement made and the radiation of light received versus time. -Oxidative stress parameters measured in blood: a. Quantification of malondialdehyde and 4- hydroxyalkenals (MDA+4-HDA) by colorimetric methods. Blood levels of MDA+4-HDA are an index of lipid peroxidation. b. Protein carbonyl content: following the methodology of Levine. The protein carbonyl content is a marker of oxidative damage to proteins. c. Nitrites: by colorimetric method. Levels of nitrites formed after reaction of reactive nitrogen species with macromolecules are used as a marker of nitrosative stress. d. Total antioxidant activity (TAS): measuring the ability of plasma to inhibit the oxidation of 2,2?-Azino-bis-(3-ethyl-benzthiazoline-6-sulfonic acid) (ABTS) by metamyoglobin and hydrogen peroxide to form the radical cation ABTS? +. e. Superoxide dismutase activity (SOD): calculating the inhibition ratio of reduction of cytochrome C by the superoxide radical (? O2-), determined at 550 nm. f. Catalase activity (CAT): by following the decrease in the concentration of hydrogen peroxide (H2O2). g. Glutathione reductase activity (GRD): by oxidation of NADPH to NADP+ in the presence of oxidized glutathione, following the decrease in absorbance at ? = 340 nm for 3 minutes, as described by Goldberg and Spooner. h. Glutathione peroxidase activity (GP): using the colorimetric kit (Oxis Research, Foster CA) that follows the steady decline in the concentration of NADPH as reduced glutathione levels remain constant. i. Melatonin: using the melatonin radioimmunoassay kit (DLD Diagnostika GmbH, Hamburg, Germany). -Visual function: best corrected visual acuity evaluated by Early Treatment Diabeic retinopahty Study (ETDRS) scale or low vision ones, Funduscopy evaluation, Macular and Retinal Nerve Fiber Layer thicknesses measured by Spectral Domain Optical Coherence Tomography using Spectralis OCT (Heidelberg, Germany), at the different macular areas described by ETDRS, Electoretinogram (ERG) and automated perimetry. |
Calidad del sueño, valorada mediante los cuestionarios de calidad de sueño de Pittsburg (Pittsburg Sleep Quality Index, PSQI), Escala de Somnolencia de Epworth y cuestionario de tipología circadiana de Horne & Ostberg. - Calidad de vida, valorada mediante los cuestionarios de calidad de vida de NEI-VFQ-25 - Ritmo sueño-vigilia, monitorizado mediante un actímetro que se coloca en la muñeca del paciente, al estilo de un reloj, registrando la cantidad de movimiento realizado y la radiación lumínica recibida en función del tiempo. - Párametros de estado oxidativo que se determinarán en plasma: a. Cuantificación de malonildialdehido y 4-hidroxialquenales (MDA+4- HDA): mediante método colorimétrico. Las concentraciones de MDA+4-HDA son un indicador del grado de peroxidación de los lípidos. b. Restos carbonilo de las proteínas: siguiendo la metodología de Levine. Los restos carbonilo son un marcador del daño oxidativo a las protéinas. c. Nitritos: mediante método colorimétrico. Los niveles de nitritos formados tras la reacción de las especies reactivas de nitrógeno con las macromoléculas de la célula permiten cuantificar el estado nitrosativo de la misma. d. Actividad total antioxidante (TAS): midiendo la capacidad del plasma de inhibir la oxidación del 2,2'-azino-bis-(ácido 3-etil-benzotiazolina-6-sulfónico) (ABTS) por la metamioglobina y peróxido de hidrógeno para formar el catión radical ABTS?+. e. Actividad de la superóxido dismutasa (SOD): calculando la inhibición del ratio de reducción del citocromo C por el radical superóxido (?O2-), determinado a 550 nm. f. Catalasa (CAT): siguiendo el descenso en la concentración de peróxido de hidrógeno (H2O2). g. Glutatión reductasa (GRd), mediante la oxidación de NADPH a NADP+, en presencia de glutation oxidado, siguiendo el descenso en la absorbancia a ?=340 nm durante 3 minutos, como describieron Goldberg y Spooner. h. Glutatión peroxidada (GP): observando el continuo descenso en la concentración de NADPH mientras los niveles de glutatión reducido se mantienen constantes. La medición se realizará utilizando el kit colorimétrico (Oxis Research, Foster CA). i. Melatonina: se realizará mediante el kit de radioinmunoensayo de melatonina (DLD Diagnostika GmbH, Hamburg, Alemania). - Función visual, valorada mediante test de AV con optotipos ETDRS u optotipos de baja visión, evaluación del Fondo de Ojo mediante fundoscopia y OCT de dominio espectral utilizando el Spectralis OCT, (Heidelberg, Alemania) macular y de nervio óptico valorando las diferentes áreas descritas en el ETDRS y el espesor de la capa de fibras nerviosas de la retina peripapilar, Electrorretinograma (ERG) y perimetría automatizada. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
During the 13 weeks of the follow up time. For more information check the schedule of events |
Durante las 13 semanas del período de seguimiento. Para más información consultar el protocolo |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Last patient last visit |
Última visita del último paciente reclutado en el estudio |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |