Chronic Fatigue SyndromePhase 4NCT00498485
Use of Xyrem to Improve Sleep in Chronic Fatigue Syndrome
A Phase 4 study testing Sodium Oxybate in people with Chronic Fatigue Syndrome, run by University of Medicine and Dentistry of New Jersey at 1 site in United States.
Trial summary
Chronic fatigue syndrome is a disabling illness for which there is no specific treatment. As a group, CFS patients have disturbed sleep with frequent arousals and the sense of not having slept upon awakening. Read more about this study
- Who is it for?
- Ages 21 to 65 years
- Conditions the study is for
- Chronic Fatigue Syndrome
- What is being tested?
- Sodium Oxybate
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 17 participants
- Where
- 1 siteUnited States
- Study dates
- May 2007to Dec 2008
- 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
- I have CFS
Who cannot join
- I do not meet the above criteria
- I have a lifelong history of fatigue
- I have Fibromyalgia
- I have hypertension
- I am pregnant or breastfeeding
Trial locations and contacts
1 site in 1 country.
United States1 site
UMDNJ - Pain & Fatigue Study Center, ADMC 1618
Newark, New Jersey, 07101
About this study
Official title: Phase IV - A Trial of Xyrem in the Treatment of Chronic Fatigue Syndrome.
Chronic fatigue syndrome is a disabling illness for which there is no specific treatment. As a group, CFS patients have disturbed sleep with frequent arousals and the sense of not having slept upon awakening. Xyrem (Sodium oxybate) is known to improve deep sleep and so may reduce the sleep disturbances of CFS leading to better sleep with less fatigue. Its ability to produce the rapid onset of deep sleep is a reason it became a street drug, but its availability is currently limited via distribution through a single centralized pharmacy. Xyrem has been successfully used based on results from a study on patients with fibromyalgia (FM), an ailment closely resembling CFS. However, in that study, the researchers provided no information as to whether patients had FM alone or FM plus CFS. Thus, it is not clear from this study just which patient may be helped. I have prescribed Xyrem for patients who have both FM and CFS with good results. In this study, funded by the company that makes Xyrem, I propose testing the drug's efficacy on patients with CFS alone - that is, they do not have fibromyalgia.
Volunteers for this study will complete paper and pencil questionnaires about their symptoms as well as a computerized test to assess their degree of brain fog. They will then be randomly assigned to one of two groups, placebo or drug. Volunteers will not know what group they are in until the end of the study. Only the drug group will receive the medication. The placebo group will receive a substance that looks identical to the real medicine but with no active ingredients. The medication comes as a liquid and patients will start taking an initial dose about 30 min before they expect to sleep. If subjects awaken after less than 5 hrs of sleep, they will take a second dose. If they sleep more than 5 hrs, they will be told to skip taking the second dose. We will call patients weekly to see how they are doing on the "drug." If they have tolerable side effects or report significant improvement, we will maintain the dose. But if patients report no effect of treatment, the dosage will be incremented by 1 ml per week until good sleep is achieved or a predetermined maximum is reached.
Read the detailed description
Medically unexplained fatigue occurs in about 5% of the population with 10% of that number fulfilling formal case definitions for chronic fatigue syndrome1. Medically unexplained fatigue is a major problem for both patient and practitioner - for both because there is no effective FDA-approved treatment for the symptom. One major problem for these patients is unrefreshing sleep. Formal sleep studies show reduced total sleep time and reduced sleep efficiency compared to controls.2;3 We are currently in the early stages of an NIH-funded grant designed to study cytokines during sleep. Preliminary results support awake time for patients relative to controls, producing a decreased sleep efficiency. These data lead to our working hypothesis that the problem of severe daytime fatigue is due to a previously unappreciated form of sleep pathology related to sleep fragmentation.
Patients with medically unexplained pain also complain of disturbed sleep. Sodium oxybate has been tested on patients with this complaint who fulfill a formal case definition for fibromyalgia and has found to reduce symptoms and improve sleep quality.4 Specifically, six of 7 pain/fatigue scores (overall pain, pain at rest, pain during movement, end of day fatigue, overall fatigue, and morning fatigue) were relieved by 29% to 33% with sodium oxybate, compared with 6% to 10% relief with placebo (p < 0.005). Alpha intrusion indicative of disturbed sleep, sleep latency, and rapid-eye-movement sleep were significantly decreased, while slow-wave (stage 3/4) sleep was significantly increased, compared with placebo (p < 0.005). Two of the 5 subjective sleep related variables were significantly different from placebo: morning alertness (improved by 18% with sodium oxybate, compared with 2% for placebo; p = 0.0033) and quality of sleep (improved by 33% and 10%, respectively; p = 0.0003).
Importantly, approximately 40% of patients in my study group fulfill case definitions simultaneously for CFS and FM. Since we do not know if patients in either sodium oxybate treatment trial had CFS, we cannot be sure whether efficacy was specific for FM or instead may have occurred due to the fact that a large representation of CFS had occurred.
An unpublished Phase II randomized double-blind placebo controlled trial in FM, done by Jon Russell and colleagues in Dallas and presented at the 2005 meeting of the American College of Rheumatology, reported substantial symptom improvement with statistically significant benefits in self reported pain scales and patient global impression of improvement at both doses of sodium oxybate tested compared with placebo [4.5g [9ml] total dose per night; p=0.005 and 6g [12 ml], p=0.048]. Improvement in outcome variables was 34.5% at the 4.5g and 27.3% at the 6g compared to 12.5% in the placebo group.
I have prescribed sodium oxybate in my own practice for patients who have both CFS and FM with good results. Anecdotally, patients reporting less pain also reported better quality sleep and less fatigue upon awakening. This has led me to hypothesize that sodium oxybate will reduce fatigue in patients with CFS alone (i.e., without also having FM).
To test this hypothesis, I propose doing a double blind, placebo controlled trial of sodium oxybate in 30 patients who fulfill a formal case definition for chronic fatigue syndrome and who do not also have FM.
- Conditions
- Chronic Fatigue Syndrome
- Being tested
- Placebo, Sodium Oxybate
- Keywords
- chronic, fatigue, pain, sleep, xyrem, must have chronic fatigue syndrome, no hypertension, no sleep apnea
- Medical subject headings
- Fatigue Syndrome, Chronic, Bronchiolitis Obliterans Syndrome, Fatigue, Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Subjects will be randomly assigned to either placebo or drug. The medication and the placebo come as a liquid and patients will start taking an initial dose about 30 min before they expect to sleep. If subjects awaken after less than 5 hrs of sleep, they will take a second dose. If they sleep more than 5 hrs, they will skip the second dose. We will call patients weekly to see how they are doing . If they have tolerable side effects or report significant improvement, we will maintain the dose. But if patients report no effect, the dosage will be incremented by 1 ml per week until good sleep is achieved or a predetermined maximum is reached.
Sodium OxybateDrug
Also called Xyrem
Subjects will be randomly assigned to either placebo or drug. The medication and the placebo come as a liquid and patients will start taking an initial dose about 30 min before they expect to sleep. If subjects awaken after less than 5 hrs of sleep, they will take a second dose. If they sleep more than 5 hrs, they will skip the second dose. We will call patients weekly to see how they are doing . If they have tolerable side effects or report significant improvement, we will maintain the dose. But if patients report no effect, the dosage will be incremented by 1 ml per week until good sleep is achieved or a predetermined maximum is reached.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Patients were randomized and these received placebo Receives: Drug: Placebo |
| Sodium Oxybate | Active comparator | Patients were randomized and these received the active drug Receives: Drug: Sodium Oxybate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Global Assessment of Change
A count was made of subject responses on a Patient Assessment of Change questionnaire where scores went from +2 [much better] thru 0 [no change] to -2 [much worse]
Measured: 6 weeks
Self Reported Assessment of Sleep
Subjects were asked to provide their input as to the quality of their sleep over the past week
Measured: Assessed at week 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jul 2007 (estimated)
- Study startMay 2007
- Primary completionDec 2008
- Study completionDec 2008
Why it stopped: Withdrawal of support.
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 Chronic Fatigue SyndromeStudies of the same condition, open and under way.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Medicine and Dentistry of New Jersey
- Sponsor type
- University, hospital or other
- Collaborators
- Jazz Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Benjamin Natelson, MD, Principal investigator, Rutgers, The State University of New Jersey
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00498485
- Sponsor's protocol ID
- 0120060315
- Status last verified
- Feb 2016
- First submitted
- 2 Jul 2007
- Last updated
- 19 May 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase IV - A Trial of Xyrem in the Treatment of Chronic Fatigue Syndrome.
- ClinicalTrials.gov ID
- NCT00498485
- Acronym / sponsor ID
- 0120060315
- Conditions
- Chronic Fatigue Syndrome
- Keywords
- chronic, fatigue, pain, sleep, xyrem, must have chronic fatigue syndrome, no hypertension, no sleep apnea
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Withdrawal of support.
- Enrolment
- 17 participants (actual)
- Lead sponsor
- University of Medicine and Dentistry of New JerseyUniversity, hospital or other
- Collaborators
- Jazz Pharmaceuticals
- Study start
- May 2007
- Primary completion
- Dec 2008 (actual)
- Study completion
- Dec 2008 (actual)
- First posted
- 10 Jul 2007 (estimated)
- Results
- Posted 21 Apr 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Chronic fatigue syndrome is a disabling illness for which there is no specific treatment. As a group, CFS patients have disturbed sleep with frequent arousals and the sense of not having slept upon awakening. Xyrem (Sodium oxybate) is known to improve deep sleep and so may reduce the sleep disturbances of CFS leading to better sleep with less fatigue. Its ability to produce the rapid onset of deep sleep is a reason it became a street drug, but its availability is currently limited via distribution through a single centralized pharmacy. Xyrem has been successfully used based on results from a study on patients with fibromyalgia (FM), an ailment closely resembling CFS. However, in that study, the researchers provided no information as to whether patients had FM alone or FM plus CFS. Thus, it is not clear from this study just which patient may be helped. I have prescribed Xyrem for patients who have both FM and CFS with good results. In this study, funded by the company that makes Xyrem, I propose testing the drug's efficacy on patients with CFS alone - that is, they do not have fibromyalgia.
Volunteers for this study will complete paper and pencil questionnaires about their symptoms as well as a computerized test to assess their degree of brain fog. They will then be randomly assigned to one of two groups, placebo or drug. Volunteers will not know what group they are in until the end of the study. Only the drug group will receive the medication. The placebo group will receive a substance that looks identical to the real medicine but with no active ingredients. The medication comes as a liquid and patients will start taking an initial dose about 30 min before they expect to sleep. If subjects awaken after less than 5 hrs of sleep, they will take a second dose. If they sleep more than 5 hrs, they will be told to skip taking the second dose. We will call patients weekly to see how they are doing on the "drug." If they have tolerable side effects or report significant improvement, we will maintain the dose. But if patients report no effect of treatment, the dosage will be incremented by 1 ml per week until good sleep is achieved or a predetermined maximum is reached.
Detailed description
Medically unexplained fatigue occurs in about 5% of the population with 10% of that number fulfilling formal case definitions for chronic fatigue syndrome1. Medically unexplained fatigue is a major problem for both patient and practitioner - for both because there is no effective FDA-approved treatment for the symptom. One major problem for these patients is unrefreshing sleep. Formal sleep studies show reduced total sleep time and reduced sleep efficiency compared to controls.2;3 We are currently in the early stages of an NIH-funded grant designed to study cytokines during sleep. Preliminary results support awake time for patients relative to controls, producing a decreased sleep efficiency. These data lead to our working hypothesis that the problem of severe daytime fatigue is due to a previously unappreciated form of sleep pathology related to sleep fragmentation.
Patients with medically unexplained pain also complain of disturbed sleep. Sodium oxybate has been tested on patients with this complaint who fulfill a formal case definition for fibromyalgia and has found to reduce symptoms and improve sleep quality.4 Specifically, six of 7 pain/fatigue scores (overall pain, pain at rest, pain during movement, end of day fatigue, overall fatigue, and morning fatigue) were relieved by 29% to 33% with sodium oxybate, compared with 6% to 10% relief with placebo (p < 0.005). Alpha intrusion indicative of disturbed sleep, sleep latency, and rapid-eye-movement sleep were significantly decreased, while slow-wave (stage 3/4) sleep was significantly increased, compared with placebo (p < 0.005). Two of the 5 subjective sleep related variables were significantly different from placebo: morning alertness (improved by 18% with sodium oxybate, compared with 2% for placebo; p = 0.0033) and quality of sleep (improved by 33% and 10%, respectively; p = 0.0003).
Importantly, approximately 40% of patients in my study group fulfill case definitions simultaneously for CFS and FM. Since we do not know if patients in either sodium oxybate treatment trial had CFS, we cannot be sure whether efficacy was specific for FM or instead may have occurred due to the fact that a large representation of CFS had occurred.
An unpublished Phase II randomized double-blind placebo controlled trial in FM, done by Jon Russell and colleagues in Dallas and presented at the 2005 meeting of the American College of Rheumatology, reported substantial symptom improvement with statistically significant benefits in self reported pain scales and patient global impression of improvement at both doses of sodium oxybate tested compared with placebo [4.5g [9ml] total dose per night; p=0.005 and 6g [12 ml], p=0.048]. Improvement in outcome variables was 34.5% at the 4.5g and 27.3% at the 6g compared to 12.5% in the placebo group.
I have prescribed sodium oxybate in my own practice for patients who have both CFS and FM with good results. Anecdotally, patients reporting less pain also reported better quality sleep and less fatigue upon awakening. This has led me to hypothesize that sodium oxybate will reduce fatigue in patients with CFS alone (i.e., without also having FM).
To test this hypothesis, I propose doing a double blind, placebo controlled trial of sodium oxybate in 30 patients who fulfill a formal case definition for chronic fatigue syndrome and who do not also have FM.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboPatients were randomized and these received placebo |
| Sodium Oxybate | Active comparator | Drug: Sodium OxybatePatients were randomized and these received the active drug |
Who may qualify
- Ages
- 21 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- I have CFS
Key exclusion criteria (5 listed)
- I do not meet the above criteria
- I have a lifelong history of fatigue
- I have Fibromyalgia
- I have hypertension
- I am pregnant or breastfeeding
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 |
|---|---|---|
| PlaceboSubjects will be randomly assigned to either placebo or drug. The medication and the placebo come as a liquid and patients will start taking an initial dose about 30 min before they expect to sleep. If subjects awaken after less than 5 hrs of sleep, they will take a second dose. If they sleep more than 5 hrs, they will skip the second dose. We will call patients weekly to see how they are doing . If they have tolerable side effects or report significant improvement, we will maintain the dose. But if patients report no effect, the dosage will be incremented by 1 ml per week until good sleep is achieved or a predetermined maximum is reached. | Drug | Placebo |
| Sodium OxybateAlso: XyremSubjects will be randomly assigned to either placebo or drug. The medication and the placebo come as a liquid and patients will start taking an initial dose about 30 min before they expect to sleep. If subjects awaken after less than 5 hrs of sleep, they will take a second dose. If they sleep more than 5 hrs, they will skip the second dose. We will call patients weekly to see how they are doing . If they have tolerable side effects or report significant improvement, we will maintain the dose. But if patients report no effect, the dosage will be incremented by 1 ml per week until good sleep is achieved or a predetermined maximum is reached. | Drug | Sodium Oxybate |
Primary outcome
Global Assessment of Change
Time frame: 6 weeks
A count was made of subject responses on a Patient Assessment of Change questionnaire where scores went from +2 [much better] thru 0 [no change] to -2 [much worse]
Self Reported Assessment of Sleep
Time frame: Assessed at week 6
Subjects were asked to provide their input as to the quality of their sleep over the past week
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 May 2016.
- 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.
Benjamin Natelson, MD principal investigator
Rutgers, The State University of New Jersey
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 Sodium Oxybate in people with Chronic Fatigue Syndrome, run by University of Medicine and Dentistry of New Jersey 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 5 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: stopped early, as of the sponsor's last update on 19 May 2016. 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. Some participants in this study may receive a placebo. 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 21 Apr 2016). 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?
Global Assessment of Change (time frame: 6 weeks). The study lists 2 primary outcomes in all. 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 19 May 2016.