Use of Xyrem to Improve Sleep in Chronic Fatigue Syndrome
| Status: | Terminated |
|---|---|
| Conditions: | Neurology |
| Therapuetic Areas: | Neurology |
| Healthy: | No |
| Age Range: | 21 - 65 |
| Updated: | 5/20/2016 |
| Start Date: | May 2007 |
| End Date: | December 2008 |
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.
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.
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.
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.
Inclusion Criteria:
• I have CFS
Exclusion Criteria:
- 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
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