Clinical trial NCT02798367: Melatonin 3mg and 5mg Compared to Cognitive Behavioral Therapy for Insomnia (CBT-I) in the Treatment of Insomnia
Official title: National, Phase II/III, Multicenter, Randomized, Double-blind, Controlled, Parallel,Effect of Melatonin 3mg and 5mg Plus Cognitive Behavioral Therapy for Insomnia (CBT-I) Compared to the CBT-I Alone in the Treatment of Insomnia Disorder
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Insomnia Disorder
Keywords: insomnia
cognitive behavioral therapy for insomnia
melatonin
Lead sponsor: Ache Laboratorios Farmaceuticos S.A.
Sponsor class: INDUSTRY
First posted: 2016-06-14
Enrollment: 307
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: National clinical trials, phase II/III, combined in two stages, randomized, double-blind, controlled, parallel, study of superiority, in which three hundred and seven (307) participants of both sexes, aged equal or more than 55 years will be randomly allocated to one of three treatment groups. In the first stage. The group 01 will use Melatonin 3mg plus CBT-I, the group 02 will use Melatonin 5mg plus CBT-I and the group 03 will use CBT-I plus placebo.

Based on the results of an interim analysis will be making a decision on whether to proceed with the study and, if so, on which the doses will be selected for the second stage of the study, to be better studied. The final analysis of the treatments, melatonin in the selected dose plus CBT-I versus CBT-I alone and placebo, will include participants from both stages.

Detailed description: The treatment of insomnia disorder can be accomplished through pharmacological and nonpharmacological approaches. Behavioral techniques of Sleep Hygiene and Stimuli control are the most used. The Sleep hygiene is a psychoeducational intervention that teaches patients to prevent external or environmental factors generate adverse effects and harmful to sleep. The stimulus control technique is based on five instructions that encourages the patient to establish a proper sleep-wake rhythm and strengthens the links between the way for a quick sleep and well established. Melatonin is a hormone that participates in the regulation of the sleep-wake cycle, which is produced and secreted primarily by the pineal gland in the dark period and prepares the individual to sleep. Melatonin is involved in the induction of sleep and has proven therapeutic action in insomnia disorders, and may also play a role in the circadian timing system of mammals and serve as a marker for "biological clock".

Eligibility criteria: Inclusion Criteria:

* Fulfill the criteria for insomnia disorder, according to DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, 5th Edition);
* Complaint of difficulty falling asleep;
* Ability to understand and consent their participation in this clinical study, expressed by signing the Informed Consent Form (ICF).

Exclusion Criteria:

* Any finding of clinical/physical observation or laboratory examination to be interpreted by the investigator as a risk to the inclusion of the participant in the clinical study;
* Known hypersensitivity to drug components used during the study;
* Participant have any family relationship to the second degree or bond with employees or employees of Sponsor and Sites;
* Participant has used beta-blockers (in the last 30 days prior to screening visit), psychoactive drugs or sedative effect, such as, but not limited to: sedatives (in the last 14 days prior to screening visit), hypnotics (in the last 07 days prior to screening visit), muscle relaxants (in the last 11 days prior to screening visit), antihistamines first generation (in the last 08 days prior to screening visit), and antidepressants, antiepileptics, antipsychotics, among others (in the last 30 days prior to screening visit);
* Participants diagnosed with clinical diseases that interfere with sleep, such as chronic pain, nocturia, hypothyroidism, hyperthyroidism, severe heart disease, serious neurological and psychiatric disorders according to the assessment of the investigator;
* Participants diabetics insulin dependent;
* Sleep apnea moderate to severe - AHI \> 20 (Apnoea-Hypopnoea Index) assessed by polysomnography at the baseline;
* Participants who work at night;
* Participant who has BMI ≥ 30;
* Participant score above 50 in Anxiety Inventory to assess the degree of anxiety;
* Participant with cognitive impairment, based on the result obtained in the Mini-Mental State Examination. The cognitive impairment will be considered with score below 13 points for illiterates, below 18 for participants with one to eight incomplete years of schooling, below 26 for those with education of eight or more years;
* Participant score above 20 on the Beck Inventory to assess depression;
* Abuse of alcohol or illicit drugs, according to the assessment of the investigator;
* Male participants who do not agree to use acceptable methods of contraception; 1) male participants: barrier methods, except surgically sterile (vasectomy) or participants who declare to perform sexual practices on a not to reproductive way. 2) methods of contraception for the male participant's partner: oral contraceptives, injectable contraceptives, intrauterine device (IUD), hormonal implants, hormonal patch, tubal ligation and barrier methods; except surgically sterile (bilateral oophorectomy or hysterectomy) or the menopausal for at least one year;
* Female participants who are in the reproductive age and do not agree to use acceptable methods of contraception (oral contraceptives, injectable contraceptives, intrauterine device (IUD), hormonal implants, barrier methods, hormonal patch and tubal ligation); except surgically sterile (bilateral oophorectomy or hysterectomy), the menopausal for at least one year and participants who declare to perform sexual practices on a not to reproductive way;
* Women in gestation period or who are breastfeeding;
* Participant who has participated in clinical trial protocols in the last twelve (12) months (CNS Resolution 251 of August 7, 1997, Part III, sub-item J), unless the investigator considers that there may be a direct benefit to the same.

Primary outcomes:
measure: Change of Sleep Latency after 21 (±2) days of the treatment.
timeFrame: 21 (±2) days
Secondary outcomes:
measure: Quality of Sleep - Pittsburgh Sleep Quality Index
timeFrame: 21 (±2) days
measure: Wellness Day - Well-Being Index-5 (WHO-5)
timeFrame: 21 (±2) days
measure: Severity of Insomnia - Insomnia Severity Index
timeFrame: 21 (±2) days
measure: Total Sleep Time - Polysomnography
timeFrame: 21 (±2) days
measure: Sleep Architecture - the length and proportion of N1(non-rapid eyes movement) stages, N2, N3 and REM
timeFrame: 21 (±2) days
measure: Sleep Efficiency - Polysomnography
timeFrame: 21 (±2) days
measure: The Latency of Persistent Sleep - Polysomnography
timeFrame: 21 (±2) days
measure: Latency of REM (rapid eyes movement) Sleep - Polysomnography
timeFrame: 21 (±2) days
measure: Satisfaction of the participants with the treatment.
timeFrame: 21 (±2) days
Other outcomes:
Locations:
city: Vitória
country: Brazil
facility: CEDOES - Centro de Diagnóstico e Pesquisa da Osteoporose do Espirito Santo.
state: Espírito Santo
city: Porto Alegre
country: Brazil
facility: Hospital de Clínicas de Porto Alegre
state: Rio Grande Do Sul
city: Campinas
country: Brazil
facility: Allergisa Pesquisa Dermato Cosmética Ltda.
state: São Paulo
city: Ribeirão Preto
country: Brazil
facility: Hospital das Clinicas da Faculdade de Medicina de Ribeirão Preto USP
state: São Paulo
city: Santo André
country: Brazil
facility: Centro de Estudos Multidisciplinar CEPES da Faculdade de Medicina do ABC
state: São Paulo
city: São Paulo
country: Brazil
facility: Dr Consulta Clinica Medica Ltda
city: São Paulo
country: Brazil
facility: Centro Paulista de Investigação Clínica e Serviços Médicos Ltda.
city: São Paulo
country: Brazil
facility: Centro de Desenvolvimento em Estudo Clínicos Brasil - CDEC Brasil
Study officials:
affiliation: Allergisa Search Dermato Cosmetic Ltda.
name: Mauro Crippa Jr.
role: PRINCIPAL_INVESTIGATOR
References: