Role of the Serotonin 2A Receptor in Women With Premenstrual Disorders: a Randomized, Double-blind, Placebo-controlled Study (L4Her-Study)
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- Change in premenstrual symptom burden
研究概览
简要总结
The investigators aim to investigate the role of the serotonin 2A receptor in women with premenstrual disorders. This study uses a double-blind, randomized, controlled design with 3 arms: Intervention 1: 10 micg LSD for ~10 days during the late luteal phase (for 3 cycles) Intervention 2: 10 micg LSD every other day for ~10 days during the late luteal phase (for 3 cycles) Control intervention: Placebo for ~10 days during the late luteal phase (for 3 cycles) Each participant will be treated in only one arm. The study employs a parallel design with three treatment arms and consists of a two-cycle observational phase followed by a three-cycle treatment phase.
详细描述
Premenstrual disorders (premenstrual syndrome (PMS) and Premenstrual Dysphoric Disorder (PMDD)) affect many women (20 - 30% for PMS and 1.2 - 6.4% for PMDD) and are associated with affective symptoms, pain, mood impairment, insomnia, loss of well-being, and productivity making it complex disorders with combined mood, physical, and cognitive symptoms.
The serotonin 2A receptor has been shown to be potentially involved in the pathophysiology of premenstrual disorders, however the mechanism remains to be investigated. Anecdotal evidence suggests that low doses of psychedelics like LSD or psilocybin, taken during the luteal phase, may help alleviate symptoms. However, this approach lacks scientific validation and requires further research. We therefore seek to investigate if repeated and targeted administration of low doses of the serotonin 2A receptor agonist LSD modulates the symptom burden in premenstrual disorders.
The study employs a parallel design with three treatment arms and consists of a two-cycle observational phase followed by a three-cycle treatment phase. Timepoints below are based on a 28-day menstrual cycle, but will be adapted based on individual menstrual cycle durations.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Known hypersensitivity to LSD
- •Current treatment for PMS/PMDD
- •Use of an oral hormonal contraceptive < 6 months.
- •Past or present bipolar or psychotic disorder, including depressive disorder with psychotic features.
- •First degree relative with a psychotic disorder.
- •Significant prodromal psychotic symptoms (Prodromal Questionnaire-16 symptoms ≥ 6).
- •Borderline personality disorder.
- •Current post-traumatic stress disorder.
- •Pregnant or breastfeeding
- •Planned pregnancy.
- •Current or recent history of significant suicide ideation or suicide behavior within the past 6 months.
- •Current substance use disorder (< 12 months) other than tobacco smoking.
- •Other illness that excludes repeated LSD administration or requires interfering medication.
- •Participation in another clinical trial (currently or within the last 30 days)
研究组 & 干预措施
10 μg LSD every day during the acute symptom phase
Participants receive 10 μg LSD daily, starting at symptom onset (or latest 7 days after ovulation) until day 3 of the following cycle for 3 menstrual cycles
干预措施: LSD 10 μg every Day (Drug)
10 μg LSD every second day during acute symptom phase
10 μg LSD every second day during acute symptom phase starting at symptom onset (or 7 days after ovulation) until day 3 of the following cycle for 3 menstrual cycles
干预措施: LSD 10 μg every other day (Drug)
Placebo Control
The subjects in the control arm will receive oral placebo over 3 cycles during the luteal phase, starting at symptom onset (or latest 7 days after ovulation) until day 3 of the following cycle.
干预措施: Placebo (Drug)
结局指标
主要结局
Change in premenstrual symptom burden
时间窗: Daily over the 5 cycle study course (average cycle duration is 28 days)
Premenstrual symptom burden measured with the Daily Record of Severity of Problems (DRSP) total score as the mean of the 5 highest symptomatic days of the 7 days before menstruation onset as mean change from baseline (the two monitored cycles before treatment start) of symptoms over all three treatment periods compared with the other study arms.
次要结局
- Montgomery-Asberg-Depression-Rating Scale (MARDS)(Ratings will be performed on day 3 of each menstural cycle, over the whole study period of 5 menstrual cycles, to retrospectively rate depressive symptoms during the premenstrual phase (based on an average cycle duration of 28 days))
- Hamilton Anxiety Rating Scale (HAM-A)(Ratings will be performed on day 3 of each menstural cycle , over the whole study period of 5 menstrual cycles to retrospectively rate anxiety symptoms during the premenstrual phase ((based on an average cycle duration of 28 days).)
- State-trait anxiety inventory (STAI)(The STAI will be repeatedly assessed 3 times per cycle (twice during the late luteal phase (cycle day 20 and 26 based on a 28-day cycle) and on day 3 after start of mensturation) over the whole study period of 5 menstrual cycles.)
- Beck Depression Inventory (BDI)(The BDI will be repeatedly assessed 3 times per cycle (twice during the late luteal phase (cycle day 20 and 26 based on a 28-day cycle) and on day 3 after start of mensturation) over the whole study period of 5 menstrual cycles.)
- Quality of Life (WHOQOL-bref)(The WHOQOL-bref will be repeatedly assessed 3 times per cycle (twice during the late luteal phase (cycle day 20 and 26 based on a 28-day cycle) and on day 3 after start of me, additionally it will be assessed at screening and once during the luteal phase)
- Menstrual pain(Menstrual pain will be assessed on menstruation days over 5 menstrual cycles (average cycle duration is 28 days).)
- Quality of Sleep(Participants are asked to rate their sleep quality daily over 5 menstrual cycles (average cycle duration is 28 days).)
- Daily mood (AMRS)(The AMRS will be administered daily over 5 menstrual cycles (average cycle duration is 28 days).)
- Female Sexual Function Index (FSFI)(The outcome will be on day 3 of each menstural cycle to retrospectively rate sexual function during the premenstrual phase over 5 menstrual cycles (average cycle duration is 28 days).)
- Concomitant Medication(Complete concomitant medication including on-demand medication during bleeding days (dysmenorrhea) will be assessed at screening and rescreening. The exact intake will be recorded daily over 5 menstrual cycles (average cycle duration is 28 days).)
- Subjective effects questionnaire (Visual Analog Scales, VAS)(Will be assessed during the first drug administration in cycle 3, latest 7 days after ovulation (average cycle duration is 28 days). Scales will be administered at 0, 0.5, 1, 2, 3, 4, 5, and 6 hours after substance administration.)
- 5-Dimensions of Altered States of Consciousness (5D-ASC)(Only once 6 hours after drug administration on the first in-house drug application (cycle 3, latest 7 days after ovulation, average cycle duration is 28 days))
- Mystical Effects Questionnaire (MEQ)(Only once 6 hours after drug administration on the first in-house drug application (cycle 3, latest 7 days after ovulation, average cycle duration is 28 days))
- List of complaints (LC)(Twice during the first in-house drug application (cycle 3, latest 7 days after ovulation, average cycle duration is 28 days) baseline (before drug administration) and 6 hours after drug administration.)
- Changes in cognition(Once during the luteal phase of an unmedicated cycle (cycle day 26 based on a 28-day cycle), once during the luteal phase of a medicated cycle (cycle day 26 based on a 28-day cycle), and once during the follicular phase of a medicated cycle.)
- Blood pressure(Will be assessed during the first drug administration in cycle 3, latest 7 days after ovulation -0.5, 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5 and 6 hours after substance administration (average cycle duration is 28 days).)
- Heart rate(Will be assessed during the first drug administration in cycle 3, latest 7 days after ovulation -0.5, 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5 and 6 hours after substance administration (average cycle duration is 28 days).)
- Expectancy as mediator for treatment effects(Baseline)
- Personality traits as mediator for treatment effects (NEO-FFI)(Baseline)
- Personality traits as mediator for treatment effects (FPI-R)(Baseline)
研究者
Friederike Holze
Head of Clinical Research
University Hospital, Basel, Switzerland