Safety and Efficacy of Lysergic Acid Diethylamide (LSD) as Treatment for Cluster Headache: a Randomized, Double-blind, Placebo-controlled Phase II Study
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Change in frequency of the cluster headache attacks
研究概览
简要总结
Background: After no official research in humans in the last 40 years, research and therapeutic uses of the serotonergic psychedelic lysergic acid diethylamide (LSD) are now re-recognized and include its use in brain research, alcoholism, anxiety associated with terminal illness, and treatment of headache disorders. Specifically, LSD has been reported to abort attacks, to decrease frequency and intensity of attacks, and to induce remission in patients suffering from cluster headache (CH).
Objective: To investigate the effects of an oral LSD pulse regimen (3 x 100 µg LSD in three weeks) in patients suffering from CH compared with placebo.
Design: Double-blind, randomized, placebo-controlled two-phase cross-over study design.
Participants: 30 patients aged ≥ 25 and ≤ 75 years with chronic or episodic CH with predictable periods lasting approximately 2 months and attacks responding to oxygen.
Main outcome measures: Changes in frequency and intensity of CH attacks assessed with a standardized headache diary Significance: CH is often rated as the most painful of all primary headaches, which not only causes significant disability, but is also associated with enormous personal, economic, and psychiatric burden. At the moment, there is no specific treatment available for CH, but serotonergic compounds represent an important drug class, especially in the abortive management of cluster attacks. However, there is a need for new treatment approaches, as CH is also often insufficiently managed with available medication. This study will evaluate the potential benefit and safety of a treatment with LSD for patients with CH.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
double-blind
入排标准
- 年龄范围
- 25 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 25 and ≤ 75 years
- •Chronic cluster headache (according to the International Headache Society (IHS) criteria) OR
- •Episodic cluster headache (according to the IHS criteria) with recurrent predictable episodes lasting approximately 2 months and expected ongoing cluster period for at least one month beyond the inclusion
- •Attacks respond to oxygen
- •Sufficient understanding of the study procedures and risks associated with the study
- •Participants must be willing to adhere to the study procedures and sign the consent form
- •Participants are willing to abstain from taking preventive and abortive medication (except from oxygen) long enough before and after the LSD/placebo treatment session to avoid the possibility of a drug-drug interaction
- •Participants are willing to refrain from taking any psychiatric medications during the experimental session period. If they are being treated with antidepressants, lithium or are taking anxiolytic medications on a fixed daily regimen, such drugs must be discontinued long enough before the LSD/placebo treatment session to avoid the possibility of a drug-drug interaction.
- •Participants must also refrain from the use of any psychoactive drugs and caffeine within 24 hours of each LSD/placebo treatment session. They must agree not to use nicotine for at least 2 hours before and 6 hours after each dose of LSD. They must agree to not ingest alcohol-containing beverages for at least 1 day before each LSD treatment session. Non-routine medications for treating breakthrough pain taken in the 24 hours before the LSD treatment session may result in rescheduling the treatment session to another date, with the decision at the discretion of the investigators after discussion with the participant.
- •Participants must be willing not to drive a traffic vehicle or to operate machines within 24 hours after LSD/placebo administration.
排除标准
- •Other forms of headache attacks (migraine, paroxysmal hemicranias, shortlasting unilateral neuralgiform headache attacks with conjunctival injection, tearing, sweating and rhinorrhea (SUNCT) or with cranial autonomic symptoms (SUNA))
- •Women who are pregnant, nursing or of child-bearing potential and are not practicing an effective means of birth control (double-barrier method, i.e. pill/intrauterine device and preservative/diaphragm)
- •Past or present diagnosis of a primary psychotic disorder. Subjects with a first degree relative with psychotic disorders are also excluded.
- •Past or present bipolar disorder (DSM-IV).
- •Current substance use disorder (within the last 2 months, DSM-V, except nicotine).
- •Somatic disorders including severe cardiovascular disease, untreated hypertension (systolic blood pressure > 160mmHg without treatment, systolic blood pressure > 140 mmHg with treatment), severe liver disease (liver enzymes increase by more than 5 times the upper limit of normal) or severely impaired renal function (estimated creatinine clearance <30 ml/min), or other that in the judgement of the investigators pose too great potential for side effects.
- •Weight < 45kg
- •Participation in another clinical trial (currently or within the last 30 days)
- •Participants taking higher steroid doses (>10mg/d) over a longer time period (>2 weeks), as this would require tapering
- •Use of immunomodulatory agents (i.e. azathioprine) in the past 2 weeks
- •Use of serotonergic antiemetics (i.e. ondansetron) in the past 2 weeks
研究组 & 干预措施
LSD, Placebo
Lysergic acid diethylamide (3 x 100 µg LSD in three weeks, per os) followed by Placebo
干预措施: Lysergic Acid Diethylamide (Drug)
LSD, Placebo
Lysergic acid diethylamide (3 x 100 µg LSD in three weeks, per os) followed by Placebo
干预措施: Placebo (Drug)
Placebo, LSD
Placebo (3 x 1 vial looking like LSD in three weeks, per os) followed by Lysergic acid diethylamide
干预措施: Lysergic Acid Diethylamide (Drug)
Placebo, LSD
Placebo (3 x 1 vial looking like LSD in three weeks, per os) followed by Lysergic acid diethylamide
干预措施: Placebo (Drug)
结局指标
主要结局
Change in frequency of the cluster headache attacks
时间窗: 8 weeks before and after pulse regimen
assessed with a standardized headache diary, within-subjects analysis
Change in intensity of the cluster headache attacks
时间窗: 8 weeks before and after pulse regimen
assessed with a standardized headache diary, within-subjects analysis
次要结局
- Episode abortion(through study completion, an average of 1 year)
- Change in duration of attacks(8 weeks after pulse regimen)
- Time to first attack after completion of pulse regimen(8 weeks after pulse regimen)
- Cumulative time with headache(8 weeks after pulse regimen)
- Acute psychological effects assessed by SCQ(10 hours after drug administration)
- Change in cluster period duration and interval between cluster periods(8 weeks after pulse regimen)
- Number of attacks requiring abortive medication(8 weeks after pulse regimen)
- Number of Attack-associated autonomic symptoms(8 weeks after pulse regimen)
- Quality of life assessed by questionnaires: 36-item short-form health survey (SF-36)(through study completion, an average of 1 year)
- Quality of life assessed by questionnaires: 5-level EuroQoL-5D (EQ-5D-5L)(through study completion, an average of 1 year)
- Quality of life assessed by questionnaires: Headache Impact Test (HIT-6)(through study completion, an average of 1 year)
- Effects on depressive /anxious symptoms assessed by questionnaires: State-trait anxiety inventory (STAI)(through study completion, an average of 1 year)
- Acute autonomic effects assessed by blood pressure(10 hours after drug administration)
- Acute psychological effects assessed by questionnaire Visual analogue scales (VAS)(10 hours after drug administration)
- Effects on depressive /anxious symptoms assessed by questionnaires: Generalized anxiety disorder-7 (GAD-7)(through study completion, an average of 1 year)
- Effects on depressive /anxious symptoms assessed by questionnaires: Hospital Anxiety and Depression Scale (HADS)(through study completion, an average of 1 year)
- Acute autonomic effects assessed by heart rate(10 hours after drug administration)
- Effects on depressive /anxious symptoms assessed by questionnaires: Beck Depression Inventory (BDI)(through study completion, an average of 1 year)
- Effects on depressive /anxious symptoms assessed by questionnaires: Patient health questionnaire-9 (PHQ-9)(through study completion, an average of 1 year)
- Acute autonomic effects assessed by body temperature(10 hours after drug administration)
- Adverse Events(through study completion, an average of 1 year)
- Acute psychological effects assessed by questionnaire 5-dimensions of altered states of consciousness(10 hours after drug administration)
- Persisting effects attributed to the LSD experience(through study completion, an average of 1 year)
- Change of attack frequency at the end of the study compared with baseline(through study completion, an average of 1 year)
- Change of attack intensity at the end of the study compared with baseline(through study completion, an average of 1 year)
- Change in attack frequency before and after pulse regimen(8 weeks after first pulse regimen)
- Change in attack intensity before and after pulse regimen(8 weeks after first pulse regimen)
- Expectancy(at screening)
- Blinding(after study days and at the end of study visit)