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Status unknownNCT02798367MorfeuUpdated Sep 3, 2020

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

A Phase 2/3 interventional study of CBT-I plus placebo and CBT-I plus Melatonin 3 mg in Insomnia Disorder, sponsored by Ache Laboratorios Farmaceuticos S.A.. Status unknown at 8 sites in Brazil. Open to participants aged 55 Years and older. Per ClinicalTrials.gov, last updated 2020-09-03.

Sponsored by Ache Laboratorios Farmaceuticos S.A. · Phase 2/3, Interventional, and Treatment

The sponsor has not verified this record recently (last verified Sep 2020), so the status shown — last known as Recruiting — may be out of date.
Phase
Phase 2/3
Study type
Interventional
Enrollment
307
Allocation
Randomized
Ages
55 Years and older
Sex
All
01

Study 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.

Read the 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".

02

Conditions studied

  • Insomnia Disorder

Keywords

  • insomnia
  • cognitive behavioral therapy for insomnia
  • melatonin
03

Who can participate

Ages eligible
55 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
04

Study design

Phase
Phase 2 / Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
307 participants (estimated)

Study arms

  • 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 · Drug: CBT-I plus Melatonin 3 mg

  • 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 · Drug: CBT-I plus Melatonin 5 mg

  • Other
    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

Interventions

  • BehavioralCBT-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)

  • DrugCBT-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.

    Also known as: Melatonin

  • DrugCBT-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.

    Also known as: Melatonin

05

What researchers measure

Primary outcomes

  1. Change of Sleep Latency after 21 (±2) days of the treatment.

    Absolute change in sleep latency (in minutes) at the end of treatment compared to baseline. Sleep latency will be assessed by polysomnography.

    Time frame: 21 (±2) days

Secondary outcomes

  1. Quality of Sleep - Pittsburgh Sleep Quality Index

    Absolute change the overall score PSQI-BR, at the end of treatment from baseline

    Time frame: 21 (±2) days

  2. Wellness Day - Well-Being Index-5 (WHO-5)

    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.

    Time frame: 21 (±2) days

  3. Severity of Insomnia - Insomnia Severity Index

    Absolute change the overall score of the Insomnia Severity Index at the end of treatment from baseline

    Time frame: 21 (±2) days

  4. Total Sleep Time - Polysomnography

    Evaluate the total sleep time by polysomnography at the end of treatment from baseline

    Time frame: 21 (±2) days

  5. Sleep Architecture - the length and proportion of N1(non-rapid eyes movement) stages, N2, N3 and REM

    Proportion of participants with sleep architecture classified as normal or abnormal, assessed by polysomnography at the end of treatment from baseline.

    Time frame: 21 (±2) days

  6. Sleep Efficiency - Polysomnography

    Sleep efficiency variation assessed by polysomnography at the end of treatment from baseline

    Time frame: 21 (±2) days

  7. The Latency of Persistent Sleep - Polysomnography

    Latency of persistent sleep variation assessed by polysomnography at the end of treatment from baseline

    Time frame: 21 (±2) days

  8. Latency of REM (rapid eyes movement) Sleep - Polysomnography

    Latency of REM sleep variation assessed by polysomnography at the end of treatment from baseline

    Time frame: 21 (±2) days

  9. Satisfaction of the participants with the treatment.

    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

    Time frame: 21 (±2) days

06

Study locations

5 of 8 sites recruiting
  • CEDOES - Centro de Diagnóstico e Pesquisa da Osteoporose do Espirito Santo.
    Vitória, Espírito Santo 29055-450, Brazil
    • Karina Oliveira · Contact
    Recruiting
  • Hospital de Clínicas de Porto Alegre
    Porto Alegre, Rio Grande Do Sul 90035-903, Brazil
    Terminated
  • Allergisa Pesquisa Dermato Cosmética Ltda.
    Campinas, São Paulo, Brazil
    • Mauro Crippa Jr. · Contact · +55 19 3789-8615
    Recruiting
  • Hospital das Clinicas da Faculdade de Medicina de Ribeirão Preto USP
    Ribeirão Preto, São Paulo 14048-900, Brazil
    • Alan Eckeli · Contact
    Recruiting
  • Centro de Estudos Multidisciplinar CEPES da Faculdade de Medicina do ABC
    Santo André, São Paulo, Brazil
    Terminated
  • Dr Consulta Clinica Medica Ltda
    São Paulo, 01141-020, Brazil
    • Tatiana Hirakawa · Contact
    Recruiting
  • Centro Paulista de Investigação Clínica e Serviços Médicos Ltda.
    São Paulo, 04266-010, Brazil
    Terminated
  • Centro de Desenvolvimento em Estudo Clínicos Brasil - CDEC Brasil
    São Paulo, Brazil
    • Dalva Poyares · Contact · +55 11 5579 0373
    Recruiting
07

Registry details

Key details

Study ID
NCT02798367
Lead sponsor
Ache Laboratorios Farmaceuticos S.A.
Responsible party
Sponsor
First posted
Jun 14, 2016
Start date
Mar 22, 2018
Primary completion
Oct 31, 2021 (estimated)
Completion
Nov 30, 2021 (estimated)
Last update
Sep 3, 2020

Study contacts

Elisangela Rorato
Contact
elisangela.rorato@ache.com.br
+55 11 2608-6130
Mauro Crippa Jr.
principal investigator · Allergisa Search Dermato Cosmetic Ltda.

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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