Verstärkung Der Therapeutischen Wirkung Von Schlafentzug Durch Modafinil - Eine Doppelblinde, Randomisierte, Placebokontrollierte Monozentrische Studie Der Phase II (Enhancing the Therapeutic Efficacy of Sleep Deprivation by Modafinil - a Double Blind, Placebo-controlled Monocentric Phase II Study)
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Improvement on the Hamilton Depression Scale (6-Item Version) from Baseline to Follow-up
研究概览
简要总结
The study aims to investigate whether the administration of the stimulant modafinil during a 40 hour sleep deprivation period in depressed patients can intensify the antidepressant effect of the sleep deprivation as assessed by a reduction in the Hamilton Depression score (HAMD, 6-item version). We postulate that this also correlates with a reduction of the polysomnographically assessed overall amount of sleep during this period.
详细描述
In about 60 % of depressed patients, sleep deprivation has an acute therapeutic effect. The effect appears within very few hours; this is different from all other antidepressant treatments. However, in most cases patients relapse after the subsequent night's sleep (Wu & Bunney 1990).
The antidepressant mechanism of action of sleep deprivation is not known as yet; several hypotheses are presented and discussed in various review articles (Wiegand 1995; Kasper & Möller 1996; Wirz-Justice & van den Hoofdakker 1999; Gillin et al. 2001; Ringel & Szuba 2001; Giedke & Schwärzler 2002). At present, the following general hypotheses are most discussed:
- Sleep deprivation exerts its effect by activating or intensifying an antidepressant "pro-cess". This "process" may be dopaminergic or serotonergic transmission, thyroid function etc.
- Sleep deprivation inactivates a hypothetic "depressiogenic" substance which is produced during sleep.
- Sleep deprivation reduces the central nervous cholinergic transmitter activity and restores the balance between cholinergic and aminergic transmitter systems.
- Sleep deprivation acts by preventing sleep during a "critical" or "vulnerable" phase of circadian rhythms; there are various chronobiological assumptions which can specify such a "critical phase".
Several studies tried to indentify predictors of response to sleep deprivation in order to clarify the mechanism of action. Among clinical predictors is a symptom pattern with "endogenous" or "melancholic" traits and the presence of pronounced diurnal variations of mood, and a behaviour pattern pointing to an elevated level of arousal or activity. Another predictor is a pronounced sleep disturbance during the baseline night. Among the many neuroendocrine and neurohumoral factors which have been studied, only elevated thyroid hormones turned out to be a predictor for response to sleep deprivation. PET and SPECT studies have convergently demonstrated an elevated metabolism in parts of the limbic system (e.g., the anterior cingulum) at baseline in responders. These findings do not yet allow conclusions with respect to the neurotransmitter systems involved.
Wiegand et al. (1993) investigated whether scheduled daytime naps can induce relapses after successful sleep deprivation therapy. The timing of the nap turned out to be a crucial factor; nap sleep duration and sleep structure during naps were less important.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Inpatients of the Psychiatric Hospital of the Technical University of Munich
- •Diagnoses: Depressive episode with somatic symptoms (ICD-10: F32.01, F32.11, F32.21) or Recurrent depressive disorder with somatic symptoms (F33.01, F33.11, F33.21) or Bipolar affective disorder, presently depressive episode with somatic syndrome (F31.31, F31.41)
- •Age 18 - 70 years
- •Hamilton Depression Score (HAMD-21) at baseline > 18
- •Women at child-bearing age have to provide a negative pregnancy test before study inclusion and have to use an effective, reliable and safe method of contraception throughout the study
- •The patient must be able to understand the explanations about the study and to understand and follow the instructions of the investigator
- •The patient is not involuntarily hospitalized under German law (§ 63 Strafgesetzbuch)
排除标准
- •Presence of psychotic symptoms ICD-10: F32.3, F33.3, F31.5)
- •Present psychiatric comorbidity (e.g. substance dependence)
- •Relevant medical conditions
- •Acute suicidality
- •History of seizures
- •Paroxysmal EEG activity
- •Contraindications against treatment with modafinil (please see the most recent product information from August 2006:
研究组 & 干预措施
Modafinil (Vigil)
"Modafinil" Arm: during the 40 h sleep deprivation period (morning until evening next day) the depressed patient receives 200 mg of Modafinil each at 12:00, 24:00 and again at 12:00 o' clock
干预措施: Modafinil (Vigil) (Drug)
Placebo
"Placebo" Arm: during the 40 h sleep deprivation period (morning until evening next day) the depressed patient receives Placebo at 12:00, 24:00 and again at 12:00 o' clock
干预措施: Placebo (Drug)
结局指标
主要结局
Improvement on the Hamilton Depression Scale (6-Item Version) from Baseline to Follow-up
时间窗: Baseline, 24 h (after sleep deprivation night), 48 h (after the first recovery night)
次要结局
- Number of responders (50% reduction on the HAMD-6) in the modafinil group versus the placebo group(Baseline, 24 h (after sleep deprivation night), 48 h (after the first recovery night))
- self-rating scale of global mental state (Befindlichkeitsskala (Bf-s)) and the Stanford Sleepiness Scale.(Baseline 24 h (after sleep deprivation night), 48 h (after the first recovery night))
- Polysomnography (among others assessing sleep onset latency, sleep efficiency, sleep states, wakefulness after sleep onset)(Baseline 24 h (after sleep deprivation night), 48 h (after the first recovery night))
- Neuropsychological battery (including Zahlenverbindungstest, California Verbal Learning Test, d2 Attention Stress Test, Farb-Wort-Interferenztest, CS fine motor task(Baseline 24 h (after sleep deprivation night), 48 h (after the first recovery night))