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Melatonin 3mg and 5mg Compared to Cognitive Behavioral Therapy for Insomnia (CBT-I) in the Treatment of Insomnia (Morfeu)

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ClinicalTrials.gov Identifier: NCT02798367
Recruitment Status : Recruiting
First Posted : June 14, 2016
Last Update Posted : November 29, 2018
Sponsor:
Information provided by (Responsible Party):
Ache Laboratorios Farmaceuticos S.A.

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.


Condition or disease Intervention/treatment Phase
Insomnia Disorder Behavioral: CBT-I plus placebo Drug: CBT-I plus Melatonin 3 mg Drug: CBT-I plus Melatonin 5 mg Phase 2 Phase 3

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".

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 307 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : March 22, 2018
Estimated Primary Completion Date : December 31, 2019
Estimated Study Completion Date : January 31, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Melatonin

Arm Intervention/treatment
Experimental: CBT-I plus Melatonin 3 mg

It's a tablet manufactured by Aché S.A., composed of melatonin 3mg. Melatonin 3mg tablet will be dispensed to 65 participants (first stage) of this group in a cartridge of 3 blisters with 10 tablets each, totalizing 30 tablets. If this arm is the best set for the second stage, more 56 participants will be randomly allocated in this group.The participant shall administer 01 tablet orally every 24 hours one hour before bedtime. The duration of treatment may be 21(±2) days.

CBT-I is a non-pharmacological effective treatment for insomnia disorder. Behavioral techniques of Sleep Hygiene and Stimuli control are the most used. The CBT-I guidelines are standardized in protocol.

Behavioral: CBT-I plus placebo
Behavioral techniques of Sleep Hygiene and Stimulus Control standardized in clinical protocol plus placebo (01 tablet, orally, always at night one hour before bedtime) for 21(±2) days)

Drug: CBT-I plus Melatonin 3 mg
Behavioral techniques of Sleep Hygiene and Stimulus Control standardized in clinical protocol plus Melatonin 3 mg (01 tablet, orally, always at night one hour before bedtime) for 21(±2) days.
Other Name: Melatonin

Experimental: CBT-I plus Melatonin 5 mg

It's a tablet manufactured by Aché S.A., composed of melatonin 5mg. Melatonin 5mg tablet will be dispensed to 65 participants (first stage) of this group in a cartridge of 3 blisters with 10 tablets each, totalizing 30 tablets. If this arm is the best set for the second stage, more 56 participants will be randomly allocated in this group.The participant shall administer 01 tablet orally every 24 hours one hour before bedtime. The duration of treatment may be 21(±2) days.

CBT-I is a non-pharmacological effective treatment for insomnia disorder. Behavioral techniques of Sleep Hygiene and Stimuli control are the most used. The CBT-I guidelines are standardized in protocol.

Behavioral: CBT-I plus placebo
Behavioral techniques of Sleep Hygiene and Stimulus Control standardized in clinical protocol plus placebo (01 tablet, orally, always at night one hour before bedtime) for 21(±2) days)

Drug: CBT-I plus Melatonin 5 mg
Behavioral techniques of Sleep Hygiene and Stimulus Control standardized in clinical protocol plus Melatonin 5 mg (01 tablet, orally, always at night one hour before bedtime) for 21(±2) days.
Other Name: Melatonin

CBT-I plus placebo

It's a tablet manufactured by Aché S.A,. composed of placebo. The participants shall administer the placebo tablets to enable the double-blind study. Placebo will be dispensed to 65 (first stage) and 56 (second stage) participants of this group and shall administer 01 tablet orally every 24 hours one hour before bedtime for 21(±2) days.

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 and well consolidated sleep. The CBT-I guidelines are standardized in clinical protocol.

Behavioral: CBT-I plus placebo
Behavioral techniques of Sleep Hygiene and Stimulus Control standardized in clinical protocol plus placebo (01 tablet, orally, always at night one hour before bedtime) for 21(±2) days)




Primary Outcome Measures :
  1. Change of Sleep Latency after 21 (±2) days of the treatment. [ Time Frame: 21 (±2) days ]
    Absolute change in sleep latency (in minutes) at the end of treatment compared to baseline. Sleep latency will be assessed by polysomnography.


Secondary Outcome Measures :
  1. Quality of Sleep - Pittsburgh Sleep Quality Index [ Time Frame: 21 (±2) days ]
    Absolute change the overall score PSQI-BR, at the end of treatment from baseline

  2. Wellness Day - Well-Being Index-5 (WHO-5) [ Time Frame: 21 (±2) days ]
    Absolute change the overall score of the WHO-5 level, in the range of 0 to 100 points, at the end of treatment from baseline.

  3. Severity of Insomnia - Insomnia Severity Index [ Time Frame: 21 (±2) days ]
    Absolute change the overall score of the Insomnia Severity Index at the end of treatment from baseline

  4. Total Sleep Time - Polysomnography [ Time Frame: 21 (±2) days ]
    Evaluate the total sleep time by polysomnography at the end of treatment from baseline

  5. Sleep Architecture - the length and proportion of N1(non-rapid eyes movement) stages, N2, N3 and REM [ Time Frame: 21 (±2) days ]
    Proportion of participants with sleep architecture classified as normal or abnormal, assessed by polysomnography at the end of treatment from baseline.

  6. Sleep Efficiency - Polysomnography [ Time Frame: 21 (±2) days ]
    Sleep efficiency variation assessed by polysomnography at the end of treatment from baseline

  7. The Latency of Persistent Sleep - Polysomnography [ Time Frame: 21 (±2) days ]
    Latency of persistent sleep variation assessed by polysomnography at the end of treatment from baseline

  8. Latency of REM (rapid eyes movement) Sleep - Polysomnography [ Time Frame: 21 (±2) days ]
    Latency of REM sleep variation assessed by polysomnography at the end of treatment from baseline

  9. Satisfaction of the participants with the treatment. [ Time Frame: 21 (±2) days ]
    Proportion of participants in each level of satisfaction category Likert 5 point (1. totally dissatisfied, 2. dissatisfied, 3. neither satisfied nor dissatisfied, 4. satisfied, 5. completely satisfied) evaluated comparing the groups at the end of treatment



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:   55 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

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): NCT02798367


Contacts
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Contact: Elisangela Rorato +55 11 2608-6130 elisangela.rorato@ache.com.br

Locations
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Brazil
CEDOES - Centro de Diagnóstico e Pesquisa da Osteoporose do Espirito Santo. Recruiting
Vitória, Espírito Santo, Brazil, 29055-450
Contact: Karina Oliveira         
Hospital de Clínicas de Porto Alegre Recruiting
Porto Alegre, Rio Grande Do Sul, Brazil, 90035-903
Contact: Denis Martinez         
Allergisa Pesquisa Dermato Cosmética Ltda. Recruiting
Campinas, São Paulo, Brazil
Contact: Mauro Crippa Jr.    +55 19 3789-8615      
Hospital das Clinicas da Faculdade de Medicina de Ribeirão Preto USP Recruiting
Ribeirão Preto, São Paulo, Brazil, 14048-900
Contact: Alan Eckeli         
Centro de Estudos Multidisciplinar CEPES da Faculdade de Medicina do ABC Recruiting
Santo André, São Paulo, Brazil
Contact: Rosa Hasan    +55 11 4993-5459      
Dr Consulta Clinica Medica Ltda Recruiting
São Paulo, Brazil, 01141-020
Contact: Tatiana Hirakawa         
Centro Paulista de Investigação Clínica e Serviços Médicos Ltda. Terminated
São Paulo, Brazil, 04266-010
Centro de Desenvolvimento em Estudo Clínicos Brasil - CDEC Brasil Recruiting
São Paulo, Brazil
Contact: Dalva Poyares    +55 11 5579 0373      
Sponsors and Collaborators
Ache Laboratorios Farmaceuticos S.A.
Investigators
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Principal Investigator: Mauro Crippa Jr. Allergisa Search Dermato Cosmetic Ltda.

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Responsible Party: Ache Laboratorios Farmaceuticos S.A.
ClinicalTrials.gov Identifier: NCT02798367     History of Changes
Other Study ID Numbers: ACH-MSZ-02-03(05/16)
First Posted: June 14, 2016    Key Record Dates
Last Update Posted: November 29, 2018
Last Verified: November 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Ache Laboratorios Farmaceuticos S.A.:
insomnia
cognitive behavioral therapy for insomnia
melatonin
Additional relevant MeSH terms:
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Melatonin
Sleep Initiation and Maintenance Disorders
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Wake Disorders
Nervous System Diseases
Mental Disorders
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Central Nervous System Depressants