CirrhosisPhase 4NCT03091738
Ramelteon for Treatment of Insomnia in Cirrhosis
A Phase 4 study testing Ramelteon Pill in people with Cirrhosis, run by Virginia Commonwealth University at 1 site in United States.
Trial summary
To study the effect of ramelteon, a melatonin receptor agonist, on sleep quality, duration and cognitive function in cirrhotics with insomnia. Patients with cirrhosis have difficulties with their sleep quality, which adversely affects their health-related quality of life. Read more about this study
- Who is it for?
- Ages 21 to 65 years
- Conditions the study is for
- Cirrhosis
- What is being tested?
- Ramelteon Pill
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Feb 2017to 1 Oct 2018
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Child class A cirrhosis proven by biopsy, radiology or endoscopic evidence of varices - Able to give informed consent
Who cannot join
- Patient unwilling to start therapy
- Allergic reactions to ramelteon in the past
- Obstructive sleep apnea
- Periodic limb movement disorder
- Moderate to severe depression
- Unable to give informed consent
Show all 12Show fewer
- Night shift workers
- Inter-continental travel within the last 4 weeks
- Renal insufficiency on dialysis
- Current alcohol or illicit drug use
- Diabetes Mellitus using insulin therapy
- Use of chronic hypnotic medications more than once per week or more than 5-6 times per month
Trial locations and contacts
1 site in 1 country.
United States1 site
Virginia Commonwealth University
Richmond, Virginia, 23298
About this study
To study the effect of ramelteon, a melatonin receptor agonist, on sleep quality, duration and cognitive function in cirrhotics with insomnia.
Patients with cirrhosis have difficulties with their sleep quality, which adversely affects their health-related quality of life. It is assumed the sleep disturbances are related to hepatic encephalopathy (HE) in these patients. However, several recent reports have indicated that this is not a perfect concordance and that cognition is not related to sleep disturbance. The mechanism for this change is not clear, although there is evidence of melatonin-delayed phase in these patients as well as difficulties with the excretion pattern of cortisol. Ghrelin is an orexigenic hormone produced by the stomach which stimulates the appetite and also has a profound effect on sleep. Our group has demonstrated a substantial alteration in ghrelin secretion in cirrhosis that correlates with poor slow-wave sleep. In healthy individuals, ghrelin injection encourages slow-wave sleep while sleep deprivation increases ghrelin levels. The role of ghrelin in the sleep disturbances of cirrhosis has not been determined. Prior studies have also lacked the use of overnight polysomnography as a tool and have relied on either actigraphy or questionnaires. There is a need for detailed mechanistic and therapeutic approaches to analyzing sleep disturbances in cirrhosis.
Read more
Also the therapy of sleep disturbance in cirrhosis is largely empirical. Prior studies have evaluated hydroxyzine which runs the risk of precipitating HE. Ramelteon is a melatonin analog that is FDA-approved for use in insomnia and will potentially be useful to restore the sleep-wake cycle in cirrhosis-associated sleep disturbance.
The investigators aim to study the impact of the FDA-approved ramelteon on the sleep quality (using questionnaires and sleep diaries) on these patients with cirrhosis.
Read the detailed description
This study will be a prospective study of patients with compensated cirrhosis This study will be divided into screening and post-ramelteon visits.
For this study, subjects with cirrhosis will be recruited from the hepatology clinic.
Screening: All subjects will come for an initial screening visit to the CRSU at which point the following procedures will be performed:
- Vitals, including BMI
- Neck circumference
- Skinfold thickness and waist-hip ratio
- Beck Depression Inventory (BDI)
- Sickness impact profile for overall HRQOL
Questionnaires regarding sleep:
- Berlin questionnaire
- STOP Bang questionnaire
- Epworth sleepiness scale (ESS) and
- Pittsburgh sleep quality index (PQSI)
Cirrhotic patients with either of the criteria below (a) neck circumference >17 inches for men and >16 inches for women (b) Positive Berlin questionnaire will be excluded because these are highly suggestive of sleep disturbances and OSA. The investigators will also exclude patients who have evidence of moderate to severe depression on Beck Depression Inventory (score ≥20) without the suicide question.
All enrolled study participants will perform 5 paper-pencil and two computerized tests of intelligence which will last approximately 35 minutes total.
RAMELTEON THERAPY:
The subjects' study chart, current medications, medical history and pregnancy testing will be assessed by sleep physicians at VCU, who will then decide if this patient would benefit from ramelteon.
The criteria used will be insomnia along with the absence of OSA by the questionnaires. Ramelteon is an FDA-approved selective melatonin receptor 1 and 2 analog indicated for use in insomnia. The dose used will be 8 mg, the lowest possible dose. If the sleep specialists believe that a particular cirrhotic patient is a candidate for this therapy, they will be clinically prescribed ramelteon after a detailed face to face visit explaining the risks and benefits. Ramelteon is not indicated in patients with severe hepatic impairment (defined as Child Class C), therefore, these patients will not be included in this study.
If the patient agrees to take the medicine, it will be dispensed through the investigational pharmacy, where it will be stored for this study. Patients will be asked to complete a medication and sleep diary for the duration of the drug therapy which will be a maximum of 15 days. Within 15 days of drug initiation, the patients will be asked to complete the sleep questionnaires again and cognitive testing similar to that described in visit 1.
- Conditions
- Cirrhosis
- Being tested
- Ramelteon Pill
- Keywords
- sleep
- Medical subject headings
- Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ramelteon PillDrug
Also called Ramelteon
Patients with compensated cirrhosis and insomnia will be provided ramelteon
| Study group | Role | What they receive |
|---|---|---|
| Ramelteon Pill | Experimental | Patients given ramelteon and re-evaluated after 15 days of therapy Receives: Drug: Ramelteon Pill |
What is being measured
The primary outcome is the main question the study is designed to answer.
Sleep Quality Evaluation
Pittsburgh Sleep Quality Index (PSQI) is a 19 item survey measuring 7 components of sleep. Component scores are summed to yield a global PSQI score. Scores range from 0 to 21 with higher scores indicate worse sleep quality.
Measured: 14 days
Secondary outcomes (2)
Daytime Sleepiness Evaluation
Epworth Sleepiness Scale asks participants to rate (on a scale of 0 to 3) their likelihood of falling asleep during 8 daily activities. Scores range from 0 to 24 with lower scores indicating less sleepiness.
Measured: 14 days
Sickness Impact Profile
Sickness Impact Profile is a 68 question assessment. Items are scored 0 (no) or 1 (yes). Scores range from 0 to 68 with higher numbers indicating worse quality of life.
Measured: 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2017
- Study start1 Feb 2017
- Primary completion1 Oct 2018
- Study completion1 Oct 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for CirrhosisStudies of the same condition, open and under way.
- More trials run by Virginia Commonwealth UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Virginia Commonwealth University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jasmohan S Bajaj, MD, Principal investigator, Virginia Commonwealth University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03091738
- Sponsor's protocol ID
- HM13968
- Other IDs
- 5R01DK087913
- Status last verified
- Mar 2021
- First submitted
- 16 Mar 2017
- Last updated
- 29 Mar 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ramelteon for Treatment of Insomnia in Cirrhosis
- ClinicalTrials.gov ID
- NCT03091738
- Acronym / sponsor ID
- HM13968
- Conditions
- Cirrhosis
- Keywords
- sleep
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Virginia Commonwealth UniversityUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 1 Feb 2017 (actual)
- Primary completion
- 1 Oct 2018 (actual)
- Study completion
- 1 Oct 2018 (actual)
- First posted
- 27 Mar 2017 (actual)
- Results
- Posted 29 Mar 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To study the effect of ramelteon, a melatonin receptor agonist, on sleep quality, duration and cognitive function in cirrhotics with insomnia.
Patients with cirrhosis have difficulties with their sleep quality, which adversely affects their health-related quality of life. It is assumed the sleep disturbances are related to hepatic encephalopathy (HE) in these patients. However, several recent reports have indicated that this is not a perfect concordance and that cognition is not related to sleep disturbance. The mechanism for this change is not clear, although there is evidence of melatonin-delayed phase in these patients as well as difficulties with the excretion pattern of cortisol. Ghrelin is an orexigenic hormone produced by the stomach which stimulates the appetite and also has a profound effect on sleep. Our group has demonstrated a substantial alteration in ghrelin secretion in cirrhosis that correlates with poor slow-wave sleep. In healthy individuals, ghrelin injection encourages slow-wave sleep while sleep deprivation increases ghrelin levels. The role of ghrelin in the sleep disturbances of cirrhosis has not been determined. Prior studies have also lacked the use of overnight polysomnography as a tool and have relied on either actigraphy or questionnaires. There is a need for detailed mechanistic and therapeutic approaches to analyzing sleep disturbances in cirrhosis.
Also the therapy of sleep disturbance in cirrhosis is largely empirical. Prior studies have evaluated hydroxyzine which runs the risk of precipitating HE. Ramelteon is a melatonin analog that is FDA-approved for use in insomnia and will potentially be useful to restore the sleep-wake cycle in cirrhosis-associated sleep disturbance.
The investigators aim to study the impact of the FDA-approved ramelteon on the sleep quality (using questionnaires and sleep diaries) on these patients with cirrhosis.
Detailed description
This study will be a prospective study of patients with compensated cirrhosis This study will be divided into screening and post-ramelteon visits.
For this study, subjects with cirrhosis will be recruited from the hepatology clinic.
Screening: All subjects will come for an initial screening visit to the CRSU at which point the following procedures will be performed:
- Vitals, including BMI
- Neck circumference
- Skinfold thickness and waist-hip ratio
- Beck Depression Inventory (BDI)
- Sickness impact profile for overall HRQOL
Questionnaires regarding sleep:
- Berlin questionnaire
- STOP Bang questionnaire
- Epworth sleepiness scale (ESS) and
- Pittsburgh sleep quality index (PQSI)
Cirrhotic patients with either of the criteria below (a) neck circumference >17 inches for men and >16 inches for women (b) Positive Berlin questionnaire will be excluded because these are highly suggestive of sleep disturbances and OSA. The investigators will also exclude patients who have evidence of moderate to severe depression on Beck Depression Inventory (score ≥20) without the suicide question.
All enrolled study participants will perform 5 paper-pencil and two computerized tests of intelligence which will last approximately 35 minutes total.
RAMELTEON THERAPY:
The subjects' study chart, current medications, medical history and pregnancy testing will be assessed by sleep physicians at VCU, who will then decide if this patient would benefit from ramelteon.
The criteria used will be insomnia along with the absence of OSA by the questionnaires. Ramelteon is an FDA-approved selective melatonin receptor 1 and 2 analog indicated for use in insomnia. The dose used will be 8 mg, the lowest possible dose. If the sleep specialists believe that a particular cirrhotic patient is a candidate for this therapy, they will be clinically prescribed ramelteon after a detailed face to face visit explaining the risks and benefits. Ramelteon is not indicated in patients with severe hepatic impairment (defined as Child Class C), therefore, these patients will not be included in this study.
If the patient agrees to take the medicine, it will be dispensed through the investigational pharmacy, where it will be stored for this study. Patients will be asked to complete a medication and sleep diary for the duration of the drug therapy which will be a maximum of 15 days. Within 15 days of drug initiation, the patients will be asked to complete the sleep questionnaires again and cognitive testing similar to that described in visit 1.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ramelteon Pill | Experimental | Drug: Ramelteon PillPatients given ramelteon and re-evaluated after 15 days of therapy |
Who may qualify
- Ages
- 21 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Child class A cirrhosis proven by biopsy, radiology or endoscopic evidence of varices - Able to give informed consent
Key exclusion criteria (12 listed)
- Patient unwilling to start therapy
- Allergic reactions to ramelteon in the past
- Obstructive sleep apnea
- Periodic limb movement disorder
- Moderate to severe depression
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ramelteon PillAlso: RamelteonPatients with compensated cirrhosis and insomnia will be provided ramelteon | Drug | Ramelteon Pill |
Primary outcome
Sleep Quality Evaluation
Time frame: 14 days
Pittsburgh Sleep Quality Index (PSQI) is a 19 item survey measuring 7 components of sleep. Component scores are summed to yield a global PSQI score. Scores range from 0 to 21 with higher scores indicate worse sleep quality.
2 secondary outcomes
Daytime Sleepiness Evaluation
Time frame: 14 days
Sickness Impact Profile
Time frame: 14 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Mar 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jasmohan S Bajaj, MD principal investigator
Virginia Commonwealth University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ramelteon Pill in people with Cirrhosis, run by Virginia Commonwealth University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Mar 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Sleep Quality Evaluation (time frame: 14 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Mar 2021.