Clarithromycin for the Treatment of Hypersomnia

NCT01146600 | Completed Phase 2 Results

• 1 other identifier: IRB00044170
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Hypersomnia; Idiopathic Hypersomnia; Narcolepsy

Keywords

Primary hypersomnia; CNS hypersomnia; hypersomnia; idiopathic hypersomnia; clarithromycin; Narcolepsy without Cataplexy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• PVT Median Reaction Time at Week 1

  week 1

• PVT Number of Lapses

  baseline, then after 1 week and 2 weeks on each study drug

• Epworth Sleepiness Scale

  baseline, then after 1 week and 2 weeks on each study drug

• FOSQ

  baseline, then after 1 week and 2 weeks on each study drug

• SF-36, Vitality Subscale

  baseline, then after 1 week and 2 weeks on each study drug

Study Arms (2)

Random Group A

EXPERIMENTAL

Subjects will be randomized to group A or group B. The order of presentation of placebo and clarithromycin will be opposite in these two groups, but investigators and subjects will remain blinded to group allocation and order of treatment presentation within the groups.

Drug: Clarithromycin followed by placebo

Random Group B

EXPERIMENTAL

Subjects will be randomized to group A or group B. The order of presentation of placebo and clarithromycin will be opposite in these two groups, but investigators and subjects will remain blinded to group allocation and order of treatment presentation within the groups.

Drug: Placebo then Clarithromycin

Interventions

Clarithromycin followed by placebo DRUG

Clarithromycin 500 mg po bid for two weeks, then one week with no medication, then matched placebo po bid for two weeks.

Also known as: Biaxin

Random Group A

Placebo then Clarithromycin DRUG

Matched placebo po bid for two weeks, then one week with no intervention, then clarithromycin 500 mg po bid for two weeks

Also known as: Biaxin

Random Group B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Lynn Marie Trotti: lead

Study Sites (1)

Emory Sleep Center

Atlanta, Georgia, 30329, United States

Location

Related Publications (2)

• Trotti LM, Becker LA, Friederich Murray C, Hoque R. Medications for daytime sleepiness in individuals with idiopathic hypersomnia. Cochrane Database Syst Rev. 2021 May 25;5(5):CD012714. doi: 10.1002/14651858.CD012714.pub2.

  PMID: 34031871 DERIVED

• Trotti LM, Saini P, Bliwise DL, Freeman AA, Jenkins A, Rye DB. Clarithromycin in gamma-aminobutyric acid-Related hypersomnolence: A randomized, crossover trial. Ann Neurol. 2015 Sep;78(3):454-65. doi: 10.1002/ana.24459. Epub 2015 Jun 30.

  PMID: 26094838 DERIVED

MeSH Terms

Conditions

Disorders of Excessive Somnolence; Idiopathic Hypersomnia; Narcolepsy

Interventions

Clarithromycin

Condition Hierarchy (Ancestors)

Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Lynn Marie Trotti, MD, MSc
• Organization: Emory University School of Medicine

lbecke2@emory.edu

404-728-4752

Study Officials

• Lynn Marie Trotti, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Neurology

Study Record Dates

• First Submitted: June 15, 2010
• First Posted: June 17, 2010
• Study Start: July 1, 2010
• Primary Completion: September 1, 2012
• Study Completion: September 1, 2012
• Last Updated: November 6, 2017
• Results First Posted: June 12, 2014

Record last verified: 2017-10

Locations

US (1)