Clarithromycin for the Treatment of Hypersomnia
Condition: Hypersomnia; Idiopathic Hypersomnia; Narcolepsy
MeSH terms: Narcolepsy; Disorders of Excessive Somnolence; Idiopathic Hypersomnia
Intervention: Clarithromycin followed by placebo; Placebo then Clarithromycin
Intervention description: Clarithromycin 500 mg po bid for two weeks, then one week with no medication, then matched placebo po bid for two weeks.; Matched placebo po bid for two weeks, then one week with no intervention, then clarithromycin 500 mg po bid for two weeks
Intervention MeSH terms: Clarithromycin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 26.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Primary hypersomnia; CNS hypersomnia; hypersomnia; idiopathic hypersomnia; clarithromycin; Narcolepsy without Cataplexy

Summary:

      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.
    

Eligibility criteria:

        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