SLEEP 2011 Abstract Supplement

B. Clinical Sleep Science III. Sleep Disorders – Insomnia
0534
FRONTAL CEREBRAL THERMAL TRANSFER AS A
TREATMENT FOR INSOMNIA: A DOSE-RANGING STUDY
Nofzinger E 1,2 , Buysse DJ 1
1
Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh,
PA, USA, 2 Cereve Inc, Allison Park, PA, USA
Introduction: A reduction in frontal metabolism from waking to sleep
is associated with restorative sleep. Frontal cerebral metabolism during
sleep correlates positively with insomnia severity. Can reducing frontal
metabolism during sleep treat insomnia? Previously, frontal cerebral
thermal transfer (FCTT) at a cool setting reduced frontal metabolism
during sleep in insomnia patients. The current study aimed to determine
if all-night FCTT in insomnia patients had a dose-dependent effect on
improving sleep onset and sleep efficiency.
Methods: In a crossover study, order randomized between patients, subjects
received all-night FCTT via a soft plastic cap fitted on the scalp
and filled with circulating water. Conditions varied in temperature of
the circulating water, and therefore, in thermal transfer intensities, and
included: no device, and device with either neutral, moderate or maximal
cooling thermal transfer intensity. 110 subjects were screened, 12
met criteria for Primary Insomnia (9 women, mean age + s.d. = 44.6 +
12.5 years) and completed the study. Healthy age- and gender-matched
subjects (n=12) served as a reference.
Results: A repeated measures ANOVA revealed linear effects of thermal
transfer intensities (2-night means) on sleep latency (p = .02; effect size
= .45) and sleep efficiency (p = .05; effect size = .36). Sleep latency and
sleep efficiency in insomnia patients in the maximum thermal transfer
condition (13 + 7 minutes and 89 + 5%, respectively) did not differ from
those of healthy age- and gender-matched sleepers (16 + 16 minutes and
89 + 7%, respectively).
Conclusion: FCTT improved sleep latency and sleep efficiency in insomnia
patients in a dose-dependent manner. In the maximum condition,
sleep values in insomnia patients did not differ from healthy controls.
Replication in a large scale clinical trial is warranted to determine if
FCTT should be considered as a treatment for insomnia.
Support (If Any): R43HL097537; Respironics Research Foundation;
MH66227; MH061566; AG20677; MH24652; RR024153
0535
A PHASE I/IIA, DOSE FINDING, DOUBLE-BLIND,
RANDOMIZED, PLACEBO CONTROLLED STUDY TO
ASSESS THE SAFETY AND EFFICACY OF SUBLINGUAL
FLUMAZENIL IN REVERSAL OF THE RESIDUAL EFFECTS
OF HYPNOTIC DRUGS (ZOLPIDEM OR BROTIZOLAM)
Peled N 1 , Katz N 3 , Segev A 2 , Pillar G 2
1
Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel, 2 Sleep Lab,
Rambam Medical Center, Technion, Haifa, Israel, 3 NICU, Wolfson
Hospital, Holon, Israel
Introduction: Background: 30% of the insomnia patients suffer from
residual morning drowsiness . Purpose: To study the safety and efficacy
(dose finding) of sublingual Flumazenil (GABA-A antidote) in reversing
the residual hypnotic effect of sleeping pills in healthy volunteers.
Methods: Methods: 20 healthy subjects slept for 1.5 hours following
sleep induction (Zolpidem , n=10; Brotizolam n=10). Upon awakening,
they underwent a physical examination and neurocognitive tests including
immediate word recall test (iWRT), Digit Symbol Substitution Test
(DSST), and mood/performance questionnaires including visual analogue
scale (VAS) to assess subjective alertness. They were then treated
by Flumazenil (0.4mg; n=10 and 1.6 mg; N=10) or placebo (n=20) and
were re-evaluated after 20min and 60 minutes. A week later, the same
procedures and evaluations were performed again.
Results: Results: All 20 volunteers (10 males, age 28.8 ± 5.7) completed
the study without any adverse events. Flumazenil was superior to placebo
by 59-93% (P