Clinical trial NCT03547661: Open-Label Placebo Treatment of Women With Premenstrual Syndrome
Official title: Open-Label Placebo Treatment of Women With Premenstrual Syndrome: A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Premenstrual Syndrome
Keywords: Premenstrual Syndrome
Open-Label Placebo Effect
randomized controlled trial
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2018-06-06
Enrollment: 150
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: PMS symptom intensity assessed by a PMS symptom diary sub sum score
timeFrame: 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)
measure: PMS symptom interference assessed by a PMS symptom diary sub sum score
timeFrame: 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 outcomes:
measure: Experience of study participation in intervention groups
timeFrame: One time assessment, up to 2 years after baseline. The interview takes between 30 and 60 minutes
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: University of Basel, Faculty of Psychology, Division of Clinical Psychology and Psychotherapy
state: Basel-Stadt
Study officials:
affiliation: University of Basel, Faculty of Psychology, Division for Clinical Psychology and Psychotherapy
name: Jens Gaab, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Kam-Hansen S, Jakubowski M, Kelley JM, Kirsch I, Hoaglin DC, Kaptchuk TJ, Burstein R. Altered placebo and drug labeling changes the outcome of episodic migraine attacks. Sci Transl Med. 2014 Jan 8;6(218):218ra5. doi: 10.1126/scitranslmed.3006175.
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citation: Schaefer M, Harke R, Denke C. Open-Label Placebos Improve Symptoms in Allergic Rhinitis: A Randomized Controlled Trial. Psychother Psychosom. 2016;85(6):373-374. doi: 10.1159/000447242. Epub 2016 Oct 15. No abstract available.
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citation: Yonkers KA, O'Brien PM, Eriksson E. Premenstrual syndrome. Lancet. 2008 Apr 5;371(9619):1200-10. doi: 10.1016/S0140-6736(08)60527-9.
citation: Frey Nascimento A, Gaab J, Degen B, Rytz M, Holder A, Sezer D, Buergler S, Meyer AH, Kirsch I, Kossowsky J, Locher C. Efficacy of open-label placebos for premenstrual syndrome: a randomised controlled trial. BMJ Evid Based Med. 2025 Mar 25:bmjebm-2024-112875. doi: 10.1136/bmjebm-2024-112875. Online ahead of print.
citation: Frey Nascimento A, Gaab J, Kirsch I, Kossowsky J, Meyer A, Locher C. Open-label placebo treatment of women with premenstrual syndrome: study protocol of a randomised controlled trial. BMJ Open. 2020 Feb 17;10(2):e032868. doi: 10.1136/bmjopen-2019-032868.