Effects of a Melatonin Receptor Agonist on Clinical Manifestations and Peripheral Biological Markers of Circadian Rhythm

Melatonin Receptor Agonist and Peripheral Biological Markers



Sponsors


Source

National Science Council, Taiwan

Oversight Info

Has Dmc

No


Brief Summary

People who have insomnia typically co-occur with mental disorders, especially anxiety and
depression. It has been documented that the melatonin phase in the depressed patients was
reached with a delay. Melatonin plays a crucial role in regulation of circadian-clock-related
gene expression.

Detailed Description

The higher values of circadian-clock-related proteins observed at day (brain and muscle aryl
hydrocarbon receptor nuclear translocator-like protein 1 and circadian locomoter output
cycles protein kaput1) and night (period circadian protein homolog 1 and cryptochrome).
Melatonin receptor type 1 (MT1) and melatonin receptor type 2 (MT2) are present in mammals
including humans and involved in sleep-wake cycle. RamelteonRMT (RMT, Rozerem®), a novel MT1
and MT2 agonist, has been approved for treatment of insomnia, and provides a strong phase
shift signal to the circadian timing system. Melatonin receptor agonists have recently become
available for treatment of sleep and psychiatric disorders; however, the effects of the
melatonin receptor agonist on peripheral biological markers of circadian rhythm are still to
elucidate. This is a non-randomized, observational study, which aims of this study is to
evaluate the effects of ramelteon RMT in melatonin level and the regulation of circadian
rhythm genes expression in patients with primary insomnia, and/or major depressive disorder
(MDD) on, or generalized anxiety disorder (GAD) with symptoms of insomnia. Forty
Participants: Participants aged 20-80 years with body mass index between 18 and 34 and
without any ambulatory problems will be recruited according to clinical judgment to take RMT
for insomnia, ages 20-80 years, body mass index between 18 and 34, without any ambulatory
problems, and be willing to write sleep diary. Primary insomnia, MDD and GAD will be as
defined by the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition Revised for
at least 3 months and a history of daytime complaint(s) associated with disturbed sleep.
Participants were administered the ramelteon RMT tablet (8 mg/Tab) by oral intake at the same
time, which is 2 hours prior to the schedule bedtime every night for eight weeks. The
peripheral blood is collected at two time points - ramelteon RMT administration week 0 and
week 8, and the melatonin, circadian-clock-related day genes (Aryl hydrocarbon receptor
nuclear translocator-like protein 1 and Circadian locomoter output cycles protein kaput1) and
night genes (circadian protein homolog 1 and cryptochrome) expression variation will be
quantified and compared to determine circadian rhythm phase shift. The expected findings are
the circadian-clock-related genes would shift to normal baseline and these genes expressions
will be the peripheral marker for evaluation of drug treatment efficacy.

Overall Status

Enrolling by invitation

Start Date

2016-01-11

Completion Date

2019-07-31

Primary Completion Date

2018-12-31

Phase

N/A

Study Type

Observational

Primary Outcome

Measure

Time Frame

Hamilton Depression Rating Scale (HDRS)
8 weeks
sleep diary
8 weeks

Secondary Outcome

Measure

Time Frame

Beck Depression Inventory (BDI)
8 weeks

Number Of Groups

1

Enrollment

40

Condition


Intervention

Intervention Type

Drug

Intervention Name


Description

Ramelteon RMT (RMT, Rozerem®), a novel MT1 and MT2 agonist, has been approved for treatment of insomnia, and provides a strong phase shift signal to the circadian timing system. Melatonin receptor agonists have recently become available for treatment of sleep and psychiatric disorders


Eligibility

Study Pop

1. Out-patients with primary insomnia and patients with major depressive disorder (MDD)
and generalized anxiety disorder (GAD) with chief complaint of insomnia or a history
of daytime complaint(s) associated with disturbed sleep. The diagnosis of MDD and GAD
will be made made according to the diagnostic criteria of the Diagnostic and
Statistical Manual of Mental Disorders (DSM-IV-TR) Revised for at least 3 months.

2. Patients are 20-80 years old, body mass index between 18 and 34, and without any
ambulatory problems.

Sampling Method

Non-Probability Sample

Criteria

Inclusion Criteria:

1. Out-patients with primary insomnia and patients with major depressive disorder (MDD)
and generalized anxiety disorder (GAD) with chief complaint of insomnia or a history
of daytime complaint(s) associated with disturbed sleep. The diagnosis of MDD and GAD
will be made made according to the diagnostic criteria of the Diagnostic and
Statistical Manual of Mental Disorders (DSM-IV-TR) Revised for at least 3 months.

2. Patients are 20-80 years old, body mass index between 18 and 34, and without any
ambulatory problems.

3. Subject is a male or a post-menopausal female. Females of childbearing potential who
are sexually active must agree to use adequate contraception, and can neither be
pregnant nor lactating from Screening throughout the duration of the study.

4. If they willing to give written informed consent and cooperative in this study. They
are willing to write sleep diary.

5. Subjective sleep latency greater than or equal to 45 minutes and a subjective total
sleep time less than or equal to 6.5 hours per night for at least 3 nights during the
week of the lead-in period.

6. Habitual bedtime is between 8:30 PM and 12:00 AM.

Exclusion Criteria:

1. Known hypersensitivity to ramelteon or related compounds, including melatonin.

2. Previously participated in a study involving ramelteon.

3. Participated in any other investigational study, and/or took any investigational drug
within 30 days or five half-lives prior to the first day of single-blind study
medication, whichever is longer.

4. Sleep schedule changes required by employment (eg, shift worker) within three months
prior to the first day of single-blind study medication, or has flown across greater
than three time zones within seven days prior to screening.

5. Participated in a weight loss program or substantially altered exercise routine within
30 days prior to the first day of single blind study medication.

6. Has ever had a history of seizures, sleep apnea, chronic obstructive pulmonary
disease, restless leg syndrome, schizophrenia, bipolar disorder, mental retardation,
or cognitive disorder.

7. History of substance use disorders, such drug addiction, drug abuse, alcohol abuse
within the past 12 months, as defined in the Diagnostic and Statistical Manual of
Mental Disorders, 4th Edition Revised and/or regularly consumes 4 or more alcoholic
drinks per day.

8. History of drug addiction or drug abuse within the past 12 months.

9. Positive hepatitis panels.

Gender

All

Minimum Age

20 Years

Maximum Age

80 Years

Healthy Volunteers

No


Overall Official

Last Name

Role

Affiliation

Kuan-Pin Su, MD PhD
Principal Investigator
China Medical University Hospital

Verification Date

2018-02-01

Lastchanged Date

2018-02-12

Firstreceived Date

2018-02-07

Responsible Party

Responsible Party Type

Principal Investigator

Investigator Affiliation

National Science Council, Taiwan

Investigator Full Name

Kuan-Pin

Investigator Title

Kuan-Pin Su


Keywords


Has Expanded Access

No

Intervention Browse

Mesh Term

Melatonin


Firstreceived Results Date

N/A

Biospec Retention

Samples With DNA

Biospec Descr

The higher values of circadian-clock-related proteins observed at day (brain and muscle aryl
hydrocarbon receptor nuclear translocator-like protein 1 and circadian locomoter output
cycles protein kaput1) and night (period circadian protein homolog 1 and cryptochrome).
Melatonin receptor type 1 (MT1) and melatonin receptor type 2 (MT2) are present in mammals
including humans and involved in sleep-wake cycle.

Firstreceived Results Disposition Date

N/A

Study Design Info

Observational Model

Other

Time Perspective

Prospective


Study First Submitted

February 7, 2018

Study First Submitted Qc

February 12, 2018

Study First Posted

February 13, 2018

Last Update Submitted

February 12, 2018

Last Update Submitted Qc

February 12, 2018

Last Update Posted

February 13, 2018


ClinicalTrials.gov processed this data on February 13, 2018

Conditions

Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov, conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions

Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied. Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase

Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions that study is seeking to answer:

In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.

In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.

In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.

In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.

These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.



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