Melatonin effects on visual and sleep patterns anomalies in subjects diagnosed with Retinitis Pigmentosa

• Register: EUCTR
• Last refreshed on: 7 January 2013
• Main ID: EUCTR2012-002436-82-ES
• Date of registration: 22/10/2012
• Prospective Registration: Yes
• Primary sponsor: Isabel Pinilla Lozano
• Public title: Melatonin effects on visual and sleep patterns anomalies in subjects diagnosed with Retinitis Pigmentosa
• Scientific title: Melatonin effects on visual and sleep patterns anomalies in subjects diagnosed with Retinitis Pigmentosa
• Date of first enrolment: 13/12/2012
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-002436-82
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Spain

Contacts

• Name: Eva López Hernández
• Affiliation: Instituto Aragonés de Ciencias de la Salud

• Name: Eva López Hernández
• Affiliation: Instituto Aragonés de Ciencias de la Salud

Key inclusion & exclusion criteria

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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 80
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

To evaluate the sleep quality in patients with Retinitis Pigmentosa

Therapeutic area: Diseases [C] - Eye Diseases [C11]

Intervention(s)

Trade Name: CIRCADIN 2 mg comprimidos de liberación prolongada
Product Name: Circadin 2 mg
Pharmaceutical Form: Prolonged-release tablet
INN or Proposed INN: Not answered
CAS Number: 73-31-4
Current Sponsor code: Not answered
Other descriptive name: MELATONIN
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2-
Pharmaceutical form of the placebo: Prolonged-release capsule
Route of administration of the placebo: Oral use

Primary Outcome(s)

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

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.

Main Objective: To establish the therapeutic effect of melatonin, orally administered, on visual and sleep disturbances in adults patients affected by Retinitis Pigmentosa.

Secondary Objective: 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)

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: NO

Secondary end point(s): NO

Secondary ID(s)

EC11-441

Source(s) of Monetary Support

Ministerio de Sanidad, Política Social e Igualdad