Narcolepsy Clinical Trial
Official title:
Clarithromycin for the Treatment of Hypersomnia
Verified date | October 2017 |
Source | Emory University |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
The term 'hypersomnia' describes a group of symptoms that includes severe daytime sleepiness
and sleeping long periods of time (more than 10 hours per night). Sometimes, hypersomnia is
caused by a problem with the quality of sleep occurring at night, for instance when nighttime
sleep is disrupted by frequent breathing pauses. In other cases, however, hypersomnia occurs
even when nighttime sleep is of good quality. These cases of hypersomnia are presumed to be a
symptom of brain dysfunction, and so are referred to as hypersomnias of central (i.e., brain)
origin.
The causes of most of these central hypersomnias are not known. However, our group has
recently identified a problem with the major brain chemical responsible for sedation, known
as GABA. In a subset of our hypersomnia patients, there is a naturally-occurring substance
that causes the GABA receptor to be hyperactive. In essence, it is as though these patients
are chronically medicated with Valium (or Xanax or alcohol, all substances that act through
the GABA system), even though they do not take these medications.
Current treatment of central hypersomnias is limited. For the fraction of cases with
narcolepsy, there are FDA-approved, available treatments. However, for the remainder of
patients, there are no treatments approved by the FDA. They are usually treated with
medications approved for narcolepsy, but sleep experts agree that these medications are often
not effective for this group of patients.
Based on our understanding of the GABA abnormality in these patients, we evaluated whether
clarithromycin (an antibiotic approved by the FDA for the treatment of infections) would
reverse the GABA abnormality. In a test tube model of this disease, clarithromycin does in
fact return the function of the GABA system to normal. The investigators have treated a few
patients with clarithromycin and most have felt that their hypersomnia symptoms improved with
this treatment.
To determine whether clarithromycin is truly beneficial for central hypersomnia, this study
will compare clarithromycin to an inactive pill (the placebo). All subjects will receive both
clarithromycin and the placebo at different times, and their reaction times and symptoms will
be compared on these two treatments to determine if one is superior. If this study shows that
clarithromycin is more effective than placebo in the treatment of hypersomnia, it will
identify a potential new therapy for this difficult-to-treat disorder.
Status | Completed |
Enrollment | 26 |
Est. completion date | September 2012 |
Est. primary completion date | September 2012 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility |
Inclusion Criteria: - Hypersomnia (meeting clinical criteria for Idiopathic hypersomnia with or without long sleep time, narcolepsy lacking cataplexy, or symptomatic hypersomnia not meeting ICSD criteria) - evidence for GABA-related abnormality, as demonstrated by in-house, in vitro assay - age > 18 - high performance liquid chromatography/liquid chromatography tandem mass spectrometry verification of the absence of exogenous benzodiazepines Exclusion Criteria: - Contraindications to use of clarithromycin (pregnancy, severe renal impairment, history of QT prolongation, hypomagnesemia, hypokalemia, bradycardia, history of myocardial infarction or cardiomyopathy, myasthenia gravis, age > 70) - Current use of cisapride, pimozide, astemizole, terfenadine, colchicines, and ergotamine or dihydroergotamine - Current use of benzodiazepines or benzodiazepine-receptor agonists - moderate or severe sleep apnea (RDI > 15/hr), severe periodic limb movement disorder (PLMI > 30/hr) - diagnosis of narcolepsy with cataplexy, as determined by cerebrospinal hypocretin levels - metabolic disorders such as anemia, severe iron deficiency, B12 deficiency, or hypothyroidism that may explain symptoms of hypersomnia |
Country | Name | City | State |
---|---|---|---|
United States | Emory Sleep Center | Atlanta | Georgia |
Lead Sponsor | Collaborator |
---|---|
Lynn Marie Trotti |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Psychomotor Vigilance Task (PVT) Reaction Time | Median reaction time on the PVT at the end of the second week of treatment. Lower values reflect faster reaction times (I.e., greater vigilance). Note that the PVT provides a median of reaction times to all stimuli (~100) presented during the 10 minute PVT test. Each subject had two PVT tests at each visit, resulting in two median values. These were averaged, and then, for the purposes of this outcome, we then obtained the MEAN across multiple subjects for each condition (baseline, clarithromycin week 2, placebo week 2) |
week 2 of each intervention | |
Secondary | PVT Median Reaction Time at Week 1 | median reaction time on the PVT at week 1 of each intervention. Lower values reflect faster reaction times (i.e., better vigilance) Note that the PVT provides a median of reaction times to all stimuli (~100) presented during the 10 minute PVT test. Each subject had two PVT tests at each visit, resulting in two median values. These were averaged, and then, for the purposes of this outcome, we then obtained the MEAN across multiple subjects for each condition (baseline, clarithromycin week 1, placebo week 1) |
week 1 | |
Secondary | PVT Number of Lapses | Number of lapses (no response for > 500 msec) on the PVT, averaged by subject across all administrations for a given drug condition (i.e. administered twice at baseline, four times on clarithromycin (twice during week 1 and twice during week 2), and four times on placebo (twice during week 1 and twice during week 2)). Higher numbers indicate worse vigilance. | baseline, then after 1 week and 2 weeks on each study drug | |
Secondary | Epworth Sleepiness Scale | Scores on the Epworth Sleepiness Scale (ESS) were averaged by subject across all administrations for a given drug condition (i.e. administered twice on clarithromycin (once during week 1 and once during week 2) and twice on placebo (once during week 1 and once during week 2)). ESS scores can range from 0 to 24. Higher scores indicate higher levels of sleepiness. |
baseline, then after 1 week and 2 weeks on each study drug | |
Secondary | FOSQ | Scores on the Functional Outcomes of Sleep Questionnaire (FOSQ) were averaged by subject across all administrations for a given drug condition (i.e. administered twice on clarithromycin (once during week 1 and once during week 2) and twice on placebo (once during week 1 and once during week 2)). Scores on the FOSQ can range from 5 to 20. Higher FOSQ scores indicate less impairment due to sleepiness. |
baseline, then after 1 week and 2 weeks on each study drug | |
Secondary | SF-36, Vitality Subscale | The SF-36 is a health outcome scale with multiple subsections. Subjects were administered the entire SF-36; this analysis is of the vitality subscore provided by this scale. Scores were averaged by subject across all administrations for a given drug condition (i.e. administered once at baseline, twice on clarithromycin (once during week 1 and once during week 2) and twice on placebo (once during week 1 and once during week 2)). The vitality subscore is calculated using four questions from the SF-36, and can range from 0 to 100. Higher scores reflect more vitality. |
baseline, then after 1 week and 2 weeks on each study drug | |
Secondary | PSQI | Scores on the Pittsburgh Sleep Quality Index (PSQI), a questionnaire based assessment of sleep quality. Scores were averaged by subject across all administrations for a given drug condition (i.e. administered twice on clarithromycin (once during week 1 and once during week 2) and twice on placebo (once during week 1 and once during week 2)). Scores on the PSQI can range from 0 to 21. Higher scores indicate poorer sleep quality. |
baseline, then after 1 week and 2 weeks on each study drug |
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT04072380 -
A Study to Evaluate Safety, and Efficacy of SUVN-G3031 (Samelisant) in Patients With Narcolepsy With and Without Cataplexy
|
Phase 2 | |
Withdrawn |
NCT03626727 -
Evaluation of the Efficacy of Sodium Oxybate (Xyrem®) in Treatment of Post-traumatic Narcolepsy and Post-traumatic Hypersomnia
|
Early Phase 1 | |
Completed |
NCT02821715 -
Safety and Efficacy of THN102 on Sleepiness in Narcoleptic Patients
|
Phase 2 | |
Completed |
NCT01789398 -
Patient Narcoleptic Treated With BF2.649 (Pitolisant) in add-on to Sodium Oxybate (HARMONY IV)
|
Phase 3 | |
Completed |
NCT01681121 -
A Study of the Safety and Effectiveness of ADX-N05 for Excessive Daytime Sleepiness in Subjects With Narcolepsy
|
Phase 2 | |
Completed |
NCT00174174 -
Provigil (Modafinil) Study by Taiwan Biotech Co.
|
N/A | |
Completed |
NCT05059223 -
A Study to Assess the Efficacy and Safety of AXS-12 (Reboxetine) in Patients With Narcolepsy
|
Phase 3 | |
Completed |
NCT04923594 -
Four-week Study of the Safety and Efficacy of NLS-2 (Mazindol Extended Release) in the Treatment of Narcolepsy
|
Phase 2 | |
Recruiting |
NCT06279247 -
Proteomics and Metabolomics of Body Fluid in Patients With Narcolepsy
|
||
Completed |
NCT04647903 -
Study to Evaluate the Abuse Liability, Pharmacokinetics, Safety and Tolerability of an Abuse-Deterrent d-Amphetamine Sulfate Immediate Release Formulation (ADAIR)
|
Phase 1 | |
Completed |
NCT03267303 -
A Study to Evaluate the Safety and Efficacy of TS-091 in Patients With Narcolepsy
|
Phase 2 | |
Completed |
NCT03173378 -
Evaluation of Academic and Professional Trajectories of Narcoleptic Patients
|
||
Completed |
NCT05055024 -
An Open Label Study of NLS-2 (Mazindol Extended Release) in Subjects With Narcolepsy
|
Phase 2 | |
Completed |
NCT01067235 -
Efficacy and Safety Study of BF2.649 and BF2.649 Add on Modafinil on Cataplexy in Patients With Narcolespy
|
Phase 3 | |
Completed |
NCT00228566 -
Study to Assess Patient Reported Outcomes With Armodafinil Treatment for Excessive Sleepiness in Adults With Narcolepsy or Obstructive Sleep Apnea/Hypopnea Syndrome
|
Phase 3 | |
Completed |
NCT00107796 -
Study of PROVIGIL ® (Modafinil) Treatment in Children and Adolescents With Excessive Sleepiness Associated With Narcolepsy
|
Phase 3 | |
Completed |
NCT00107848 -
PROVIGIL® (Modafinil) Treatment in Children and Adolescents With Excessive Sleepiness Associated With Narcolepsy or Obstructive Sleep Apnea/Hypopnea Syndrome
|
Phase 3 | |
Completed |
NCT00132873 -
Trial of Xyrem® (Sodium Oxybate) for the Treatment of Narcolepsy
|
Phase 3 | |
Enrolling by invitation |
NCT05113745 -
A Study to Assess the Long-term Efficacy and Safety of AXS-12 (Reboxetine) in Subjects With Narcolepsy
|
Phase 3 | |
Suspended |
NCT04419792 -
'A Profile of Physical Performance Variables in an Out-patient Adult Population With Narcolepsy'
|