None listed
Conditions
Brief summary
Sexual dysfunction is a significant personal and social problem for people living with a spinal cord injury (SCI). The capacity for penile erection and vaginal lubrication is preserved to some extent, either through psychogenic or reflexogenic sexual response to stimulation. However, the ability to achieve orgasm is impaired and in turn, this can negatively impact personal relationships, quality of life, sexual satisfaction, and male fertility. An understanding of the altered neural circuitry contributing to sexual dysfunction in the context of SCI is therefore necessary in order to meet an unmet need for viable therapeutics. This project will assemble evidence about spinal cord and brain involvement in the initiation and maintenance of reflexogenic and psychogenic sexual responses using functional magnetic resonance imaging (fMRI). It is important to try to understand the relative contribution of signalling in spinal cord and brain circuits and pathways to sexual arousal in males and females and to relate this to the pathophysiology of sexual dysfunction in SCI.
Interventions
Neurological examination - prior to the study visit 1, a physical examination will be conducted by a qualified SCI physician or allied health professional in order to classify the severity and degree of injury. The International Standard for Neurological Classification of Spinal Cord Injury (ISNCSCI) 2019 revision will be used to stratify participants. ISNCSCI manual work sheets then will be checked against the electronic Rick Hansen Institute (Praxis) computational algorithm (http://www.isncsci
Neurological examination - prior to the study visit 1, a physical examination will be conducted by a qualified SCI physician or allied health professional in order to classify the severity and degree of injury. The International Standard for Neurological Classification of Spinal Cord Injury (ISNCSCI) 2019 revision will be used to stratify participants. ISNCSCI manual work sheets then will be checked against the electronic Rick Hansen Institute (Praxis) computational algorithm (http://www.isncscialgorithm.com/) and classification and corrected, if necessary. Motor recovery will be measured using the ISNCSCI/AIS summed motor score. This involves testing the strength on a 0-5 scale of ten key muscle groups, 5 upper and 5 lower limbs on each side of the body. Sensory appreciation is tested on a 3-point scale in 56 dermatomes bilaterally (112 total). Both pin prick and light touch perception are tested, and scores aggregated. Anal sensory and motor functions also are examined. Participants who refuse anal exam will be classified on self- report function (abbreviated ISNCSCI exam. protocol; 2020 version). IIEF - The International Index of Erectile Function (IIEF) is a widely used, multi-dimensional self-report instrument for the evaluation of male sexual function. The IIEF meets psychometric criteria for test reliability and validity, has a high degree of sensitivity and specificity, and correlates well with other measures of treatment outcome. IIEF assessment will be conducted at each study visit. FSFI - The Female Sexual Function Index (FSFI) is a widely used, multi-dimensional self-report instrument for the evaluation of female sexual function. The FSFI meets psychometric criteria for test reliability and validity, has a high degree of sensitivity and specificity. FSFI assessment will be conducted at each study visit. FSDS - The Female Sexual Distress Scale is a validated scale of female sexual dysfunction, emphasising personal distress as an essential component of sexual (dys)function. The FSDS has been observed to provide a high degree of internal consistency, and test-retest reliability. Similarly, the scale is able to highly discriminate between sexually dysfunctional and functional women. FSDS assessment will be conducted at each study visit. DASS - The depression anxiety stress scales (DASS) have been shown to possess appropriate psychometric properties, as well as symptom severity and caseness of anxiety disorders (if any). DASS assessment will be conducted at each study visit. Neuropathic pain assessment - Participants will be asked to complete the Visual Analogue Scale (VAS), Numerical Pain Rating Scale (Lichert Scale), and The Neuropathic Pain Diagnostic Questionnaire. Neuropathic pain assessment will be conducted at each study visit. MRI sequence scans - All participants will be scanned at the Clinical & Research Imaging Centre (Dr. Jones & Partners, SAHMRI). SCI participants will be asked to void, self-catheterise or if in-dwelling catheter in situ, to empty their catheter bag. Wheel-chair dependent participants will be transferred to a bed or barouche using a pat slide, or electric hoist, as per the clinical treatment plan manual handling requirement. Hoists will be operated by a nurse or technologist. For each participant structural T-weighted, and diffusion-weighted MRI will be performed on two occasions over 2 visits. Each visit will be at least 7 days apart. MRI will be performed on a Siemens 3-tesla MAGNETOM Skyra MRI scanner (Siemens, Erlangen, Germany). Standard MRI safety screening will be performed (attached) to ensure included participants have no contraindication to MRI. Prior to the entering scan participants will be transferred to the scanner platform using a pat slide, or electric hoist, as per the clinical treatment plan manual handling requirement. Participants will be positioned and secured in a recumbent position (supine with knees in ~ 30 degrees flexion, hips and upper limbs positioned in a relaxed position) on the scanner platform. The head will be secured using foam wedges and Velcro straps. Padding will be used to stabilise the upper and lower limbs A wide elastic band may be placed across the participant’s midsection (attached on each side to the bed) to further reduce movement artefact. After satisfactory limb positioning, the vertebral column of each participant will be aligned in a neutral position. A mirror in a clear plastic frame then will be positioned to allow participants to view a rear-projection screen (positioned outside of the MRI system). An optical sensor attached to the digit will record peripheral pulse. Participants will be positioned on a phased-array spine coil, aligned and centred at the T12 vertebral level. An optical sensor will be attached to the digit to record the peripheral pulse throughout the study. Initial three-plane localizer images will be acquired and used for subsequent slice positioning. An optimized spinal fMRI sequence will then use to measure task related (stimulation paradigm) signal changes based on a combination of BOLD and SEEP contrast. Stimulation Paradigms – During each MRI, erotic films will be presented to participants to serve as an audio-visual stimulation (AVS) paradigm to elicit psychological arousal/psychogenic responses for all participants. Audio-visual stimulation (AVS) is designed to detect a neuron-active in response to erotic stimuli. Each volunteer will participate in an AVS paradigm over 2 study visits. The AVS will be repeated for fMRI interrogation of spinal cord and brain tissue. AVS will be presented in two 5-minute blocks, separated by a 3-minute baseline condition (blank screen). The AVS blocks are also preceded and followed by two baseline conditions of 1.5 minutes each. The entire exposure will last for a total of 16 minutes. Before the study, participants will be informed that they will be asked about their levels of mental and physical sexual arousal. For these purposes, mental sexual arousal (MSA) is defined as feelings and mental imagery associated with the desire and motivation to engage in sexual behaviors, while physical sexual arousal (PSA) was defined as perceived physical changes such as vaginal lubrication. Subjects will be asked to rate these measures on a scale ranging from 1 (very little or no sexual arousal) to 10 (greatest possible sexual arousal) following the AVS paradigm The erotic films chosen for AVS may depict heterosexual couples engaged in sex play, vaginal sexual intercourse, and oral sex. Each participant will be provided with headphones to enable two-way communication and the transmission of the audio component of the AVS. LGBTQ+ participants will be shown films that aligns with their sexual preference and/or orientation of erotic film(s). Due to the sensitive nature of the study participants will be given maximal privacy, cameras will be switched off, and room and magnet bore lighting dimmed.
Sponsors
South Australian Health and Medical Research Institute
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Diagnosis
Masking
Blinded (masking used) (Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
SCI participants (Cohort 1) • Have a traumatic or non-traumatic SCI or disease, or a spinal cord syndrome (Central Cord Syndrome, Brown-Sequard Syndrome, Anterior Cord Syndrome) > 2 years post injury. • Have complete or incomplete SCI, and Grade A, Grade B, or Grade C classification confirmed on physical examination, conductance in accordance with the International Standard for the Neurological Classification of SCI (ISNCSCI) 2019 revision. • Have neurological level between C4 and T12 on physical examination (ISNCSCI 2019 revision); • Are medically stable and have no contraindication to MRI in the opinion of the treating physician; • Are agreeable to answer questions about their sexuality, mental and physical arousal. • Are able to abstain from taking sexual enhancing medications such as sildenafil (Viagra), tadalafil (cialis) and vardenafil (Levitra, or BP101 for at least 72 hours prior to each study visit Able-bodied participants (Cohort 2) • Have no medical history of traumatic or non-traumatic SCI, or spinal cord syndrome • Medically stable (in the opinion of the Study Doctor). • Be willing to answer questions about your sexuality and individual levels of mental and physical arousal • Are able to abstain from taking sexual enhancing medications such as sildenafil (Viagra), tadalafil (cialis) and vardenafil (Levitra, or BP101 for at least 72 hours prior to each study visit
Exclusion criteria
• Have medical history of stroke, traumatic brain injury (TBI), Parkinson’s Disease, Multiple sclerosis, brachial plexus lesion, syrinx, or any other serious neurological condition; • Have medical history of malignancy, psychiatric illness, or illicit drug-dependence; • Have active osteomyelitis of vertebral bone, Paget’s disease, or severe spinal deformity; • Have contraindication(s) to fMRI imaging; (e.g., poorly controlled spasticity, autonomic dysreflexia, pressure ulcer(s) or another medical condition) advised by the treating physician; • Have participated in investigational drug study within 30 days of enrolment; • Have in situ instrumentation (carbon fibre, or metal fixation) incompatible with fMRI in the opinion of the radiologist. • Are considered unwilling, unable or unlikely to comply with the study protocol • Have English language competency insufficient to understand research procedures, or are unable to provide informed consent.
Outcome results
None listed