Open-Label Placebo Treatment of Women With Premenstrual Syndrome

Study Overview
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Brief Summary
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This study aims to investigate the effect of an open-label placebo intervention on premenstrual syndrome (PMS) complaints. Women who suffer from moderate to severe PMS will be randomly allocated to three groups: to a treatment as usual group, an open-label placebo group, and an integrative open-label placebo group. Participants of all groups will conclude a prospective PMS screening for one menstrual cycle. Thereafter, participants of both intervention groups will obtain an openly administered placebo intervention for six weeks. Participants of the treatment as usual group will have the chance to obtain the same open-label placebo intervention after study conduct. Diverse measures will be assessed by means of a PMS symptom diary and questionnaires. Furthermore, we assess participants experiences of study participation qualitatively by means of semi-structured interviews.

Detailed Description
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Recent evidence suggests that in certain clinical conditions - such as chronic low-back pain, migraine, irritable bowel syndrome, attention deficit hyperactivity disorder, and rhinitis - placebos improve clinical outcomes even without deception. Premenstrual syndrome (PMS) is defined as clinically significant symptoms, comprising at least one emotional or physical symptom in the premenstrual phase of the menstrual cycle and which cause substantial distress or functional impairment. To date, there exists no study examining open-label placebo responses on PMS. However, PMS seems to be considerably susceptible to placebo effects: The Royal College of Obstetricians and Gynaecologists alerts to substantial placebo responses in randomized-controlled PMS trials and studies showed considerable placebo effects on PMS without any specific effect for the medication under examination. Furthermore, a myriad of distinctive therapies is described for PMS (including pharmacological and phytopharmaceutical drugs as well as complementary non-pharmacological interventions), yet partially mixed evidence is reported. Besides being considered as placebogenic, PMS symptoms are timely well-defined and delimited which further makes this condition attractive for an investigation of open-label placebo responses, as a possible amelioration can be measured in a delimited time frame. To sum up, a randomized controlled trial of an open-label placebo treatment of women with PMS allows to investigate ways to harness placebo effects ethically in clinical practice for syndromes with somatic and psychologically described characteristics.

Official Title
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Open-Label Placebo Treatment of Women With Premenstrual Syndrome: A Randomized Controlled Trial

Conditions
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Premenstrual Syndrome

Intervention / Treatment
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* Other: P-Dragees rosa Lichtenstein


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Moderate to severe PMS Between 18 and 45 years of age A regular menstrual cycle, i.e., max. +/- 3 days of difference of cycle range Menstrual cycle range not longer than 31 or shorter than 24 days Participants have a general practioner or gynaecologist to consult At least one premenstrual symptom causes the desire for a PMS treatment Exclusion Criteria: Brest feeding at the moment or during the last three months Pregnancy Failing menstruation onset in the course of two consecutive menstrual cycles An essential mental or somatic disease Drug or massive alcohol intake or of other psychoactive substances Uptake of a new medication within the last 30 days Menopause, premenopausal strain or amenorrhoea Allergy of one of the ingredients of the placebo dragées (P-Dragees rosa Lichtenstein) Women who are surgically sterilised, hysterectomised, or ovariectomised BMI above 30 Actual or recent participation in psychotherapy due to premenstrual symptoms Parallel participation in another study with investigational drugs or participation in another PMS study within the last three months

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Treatment as Usual<br>The treatment as usual (TAU) group will control for regression to the mean, spontaneous remission, natural course of disease, and the participants-provider interaction. Participants of the TAU group are allowed to continue their usual medication intake, given they are already on a stable dose (at least 30 days of intake) and the medication is not listed in the exclusion criteria. | |
| Active Comparator: Integrative Open-Label Placebo<br>The intervention will encompass an integrative administration of P-Dragees rosa Lichtenstein, which are pink placebo dragées without any active ingredient. Each dragée contents the following substances: lactose monohydrate; magnesium stearate (Ph. Eur.); microcrystalline cellulose; highly dispersed silicon dioxide; white clay, macrogol glycerolhydroxy stearate (Ph. Eur.); Arabic gum; montanglycol wax; povidone (K 25); talcum; titanium dioxide (E 171); erythrosine; aluminium salt (E 127); calcium carbonate; sucrose; glucose syrup; maize starch; macrogol 6000. All participants will be informed that the administered dragées are placebo dragées and participants will be instructed to take two dragées a day for six weeks. (Amendment regarding dosage since 08/18) | Other: P-Dragees rosa Lichtenstein<br>* Placebo dragées<br>|
| Active Comparator: Open-Label Placebo<br>The intervention will encompass an administration of P-Dragees rosa Lichtenstein, which are pink placebo dragées without any active ingredient. Each dragée contents the following substances: lactose monohydrate; magnesium stearate (Ph. Eur.); microcrystalline cellulose; highly dispersed silicon dioxide; white clay, macrogol glycerolhydroxy stearate (Ph. Eur.); Arabic gum; montanglycol wax; povidone (K 25); talcum; titanium dioxide (E 171); erythrosine; aluminium salt (E 127); calcium carbonate; sucrose; glucose syrup; maize starch; macrogol 6000. All participants will be informed that the administered dragées are placebo dragées and participants will be instructed to take two dragées a day for six weeks. (Amendment regarding dosage since 08/18) | Other: P-Dragees rosa Lichtenstein<br>* Placebo dragées<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PMS symptom intensity assessed by a PMS symptom diary sub sum score | Symptom intensity will be assessed by an intensity sub scale of the PMS symptom diary. Intensity will be rated by means of a six-level Likert scale, whereat 1 is the lowest rating of symptom intensity and 6 the highest. | Continuous measurement, starting from day 1 of the menstrual cycle (length of each cycle is on average 28 days) until the individual last day of the third menstrual cycle of each participant (assessment across three menstrual cycles in total) | 
| PMS symptom interference assessed by a PMS symptom diary sub sum score | Symptom interference will be assessed by an interference sub scale of the PMS symptom diary. Interference will be rated by means of a six-level Likert scale, whereat 1 is the lowest rating of interference and 6 the highest. | Continuous measurement, starting from day 1 of the menstrual cycle (length of each cycle is on average 28 days) until the individual last day of the third menstrual cycle of each participant (assessment across three menstrual cycles in total) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Experience of study participation in intervention groups | By means of semi-structured interviews, participants experience of participation in interventions groups of 10 women of the open-label placebo without treatment rationale group and of 10 women of the open-label placebo with treatment rationale group, who are randomly chosen out of the 50 participants of each of the intervention study groups will be assessed. | One time assessment, up to 2 years after baseline. The interview takes between 30 and 60 minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Premenstrual Syndrome, Open-Label Placebo Effect, randomized controlled trial