Clinical trial NCT04566783: Identification of Etiopathological and Clinical Factors in Persistent Genital Arousal Disorder
Official title: Identification of Etiopathological and Clinical Factors in Persistent Genital Arousal Disorder: The iPGAD-Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Restless Genital Syndrome
Sexual Arousal Disorder
Orgasmic Disorder
Psychosexual Disorder
Keywords: Persistant Genital Arousal Disorder
PGAD
Lead sponsor: Hannover Medical School
Sponsor class: OTHER
First posted: 2020-09-28
Enrollment: 52
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: * female and male patients or subjects between 18-65 years of age fulfilling the diagnostic criteria of persistent genital arousal disorder (PGAD) according to Leiblum \& Nathan (2001).
* additionally, age and education matched healthy controls.

Brief summary: Investigation of (possible etiological) factors associated with PGAD symptomatology as well as description of comorbid disorders subjects with PGAD.

Persistent genital arousal disorder (PGAD) is a presumably rare, although debilitating condition, which was first defined at the beginning of this century and has not yet found consideration by any of the international classification systems of diseases. PGAD is commonly characterized by persistent and unwanted sensations of genital arousal which are not related to subjective feelings of sexual desire or arousal. Affected patients which are predominantly women can suffer tremendously. The lack of basic research on the etiology of PGAD leads to insufficient therapeutical approaches.

Detailed description: The entire approach is of multimodal and explorative nature as only very limited information on this disease is available so far (hypotheses generating). Moreover, the aim of the study is to characterize PGAD patients in terms of their biography (e.g. trauma), comorbidities and life quality.

Clinical assessment:

* Psychological/psychiatric examination
* Neurological examination
* Gynecological/urological examination
* Laboratory assessment
* Structural and Functional Magnetic Resonance Imaging

General Hypotheses:

1. There is a morphological correlate of PGAD that affects or represents a neuronal structure leading to altered perception of genital sensation (e.g. Tarlov cysts, varices, ...).
2. There is a functional correlate of PGAD in the central nervous system (CNS) indicating a hyperfunction (excitation or disinhibition) or hypofunction (inhibition) of specific brain areas including hypothalamus, sensory cortex of the genitals and secondary brain areas, brain stem centers (e.g. raphe nuclei) and others.
3. Patients with PGAD show an elevated rate of previous pharmacological treatment with drugs that may alter the central processing of sexual/genital perception or reveal a specific pattern of comorbid diseases (e.g. affective or somatoform disorders) that may predispose other disorders such as PGAD, pain disorders etc.

Expected results and exploitation:

The proposed project will help to identify clinical and neurobiological correlates of persistent genital arousal (PGAD) and will provide

1. a deeper clinical, (neuro)psychological and (neuro)biological understanding of PGAD
2. help to identify related etiopathological mechanisms of PGAD
3. inform clinicians and (sex) therapists on diagnostic issues and promising treatment targets in PGAD derived from comprehensive clinical and experimental measures
4. stimulate further neurobiological and clinical research in the field of PGAD, leading to further national and international cooperation and applications
5. a considerable number of publications in leading scientific journals and raise awareness of a rare disease not only among all clinicians dealing with sexual problems but also general practitioners and others.

Objective(s):

Investigation of (possible etiological) factors associated with PGAD symptomatology as well as description of comorbid disorders subjects with PGAD.

Statistical Analysis:

Clinical (psychological, neurological and gynecological/urological) data is analyzed using a descriptive approach of frequencies and mean values of diverse clinical findings as well as a group comparison (patients versus healthy controls) using respective statistical analyses such as ttests, chi-square test and others after having tested for normal distribution where necessary. MRT data is analyzed using state-of-the-art special software (SPM) including group comparisons.

Sample Size Justification:

This is a cross-sectional study of a rare disease. At MHH usually 10 new patients occur per year. The investigator tries to include as many patients as possible and will probably achieve higher numbers by advertising the study and using data banks of already existing cases. Due to the presumably rare number of people affected with PGAD and the very few existing publications which are mostly case reports and the even fewer PGAD related MRI data a statistically neat sample size computing is not simple. The investigator cannot refer to prior carried out PGAD related MRI studies and to publications mentioning PGAD sample sizes. However, for MRI studies methodological work investigating the reliability of statistical effect in fMRI studies exist. An article by Thirion in 2007 shows that a sample size between 20 and 30 subjects per group is sufficient to detect statistical effects. This is also in accordance with common practice in fMRI aiming at at least 20 subject per group at which results become quite stable (Murphy \& Garavan 2004) Thus, the investigator aims at a sample size of 25 subjects per group. To account for potential dropouts (\~10%, mainly due to excessive head movement in the MRI scanner) it is planned to include approximately 30 subjects per group.

Discussion of Perceived / Expected Risks and Benefits:

When considering all exclusion criteria for MRI there are no risks known for using a magnetic resonance imaging system. Clinical and (neuro)psychological testing might be perceived stressful by some participants and therefore may lead to a temporary increase in blood pressure and/or heart rate that will normally end after testing. Clinical examination (neurological and gynecological/urological) might lead to discomfort in some participants. Besides the neurological examination which can result in uncomfortable feelings (e.g. minor pain) during the ENoG-testing and Pudendus-SEP and that will normally end immediately after testing the clinical examination is pain-free. Blood Sampling might be painful and lead to hematoma. The amount of blood is low (approx. 30ml). Any serious damage to the organism during clinical examination and blood sampling is very unlikely.

Eligibility criteria: Inclusion Criteria:

* female and male subjects
* must be between 18-65 years of age
* must fulfill the diagnostic criteria of persistent genital arousal disorder (PGAD) according to Leiblum \& Nathan (2001)
* controls must be healthy and matched in accordance with age and education.

Exclusion Criteria:

* any exclusion criteria for magnetic resonance imaging
* mental retardation
* severe somatic or mental disease such as acute psychosis, brain damage, Alzheimer disease
* severe bacterial infection requiring immediate medical treatment.

Primary outcomes:
measure: General outcome and target: Identification of clinical and neurobiological correlates of persistent genital arousal (PGAD)
timeFrame: Data collection and avaluation through study completion. Data collection (examinations) will take 1 day (max 2) per subject. Data evaluation of all collected data will take about 1 year. Publication of findings will be an ongoing process afterwards.
measure: Questionnaires: Psychological/Psychiatric, neurological and gynecological/urological assessments
timeFrame: Data collection and avaluation through study completion. Data collection (examinations) will take 1 day (max 2) per subject. Data evaluation of all collected data will take about 1 year.
measure: Clinical examinations: Psychological/Psychiatric, neurological and gynecological/urological assessments
timeFrame: Data collection and avaluation through study completion. Data collection (examinations) will take 1 day (max 2) per subject. Data evaluation of all collected data will take about 1 year.
measure: Clinical and experimental imaging (MRI, fMRI)
timeFrame: Data collection and avaluation through study completion. Data collection (examinations) will take 1 day (max 2) per subject. Data evaluation of all collected data will take about 1 year.
measure: Laboratory assessments (blood samples)
timeFrame: Data collection and avaluation through study completion. Data collection (examinations) will take 1 day (max 2) per subject. Data evaluation of all collected data will take about 1 year.
Secondary outcomes:
Other outcomes:
Locations:
city: Hannover
country: Germany
facility: Hannover Medical School
state: Lower Saxony
Study officials:
affiliation: Hannover Medical School
name: Tillmann Prof. Krüger, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Leiblum SR, Nathan SG. Persistent sexual arousal syndrome: a newly discovered pattern of female sexuality. J Sex Marital Ther. 2001 Jul-Sep;27(4):365-80. doi: 10.1080/009262301317081115.