Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622000733774
Ethics application status
Approved
Date submitted
10/05/2022
Date registered
23/05/2022
Date last updated
22/12/2022
Date data sharing statement initially provided
23/05/2022
Type of registration
Retrospectively registered

Titles & IDs
Public title
Using advanced neuroimaging techniques to measure sexual dysfunction following spinal cord injury
Scientific title
Project SCIN (Spinal Cord Injury Neurosexuality) - Developing a Biological Understanding of Sexual Health following Spinal Cord Injury using fMRI
Secondary ID [1] 307092 0
None
Universal Trial Number (UTN)
Trial acronym
Project SCIN (Spinal Cord Injury Neurosexuality)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
spinal cord injury 326251 0
Condition category
Condition code
Injuries and Accidents 323555 323555 0 0
Other injuries and accidents
Neurological 323556 323556 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.
Intervention code [1] 323547 0
Diagnosis / Prognosis
Comparator / control treatment
Sixteen (16) able-bodied, age-matched, healthy controls (8 male, 8 female) will be recruited.
Control group
Active

Outcomes
Primary outcome [1] 331313 0
Sexual function (psychogenic arousal) assessed using functional MRI (fMRI) of the spine (thoracolumbar segments) in participants with a chronic spinal cord injury.
Timepoint [1] 331313 0
At a minimum 12 months post-injury. There is no upper limit. This will be assessed in one (of a total of 2) MRI study visits.
Secondary outcome [1] 409497 0
Sexual function (psychogenic arousal) assessed using functional MRI (fMRI) of different brain regions (cortex, mid-brain and brain stem) in participants with a chronic spinal cord injury. This will be assessed as a composite outcome.
Timepoint [1] 409497 0
At a minimum 12 months post-injury. There is no upper limit. This will be assessed in one (of a total of 2) MRI study visits

Eligibility
Key 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
Minimum age
18 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key 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.

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
10/09/2021
Date of last participant enrolment
Anticipated
2/12/2024
Actual
Date of last data collection
Anticipated
30/12/2024
Actual
Sample size
Target
48
Accrual to date
29
Final
Recruitment in Australia
Recruitment state(s)
SA

Funding & Sponsors
Funding source category [1] 311399 0
Government body
Name [1] 311399 0
Lifetime Support Authority
Country [1] 311399 0
Australia
Funding source category [2] 311400 0
Charities/Societies/Foundations
Name [2] 311400 0
Neil Sachse Centre for Spinal Cord Research
Country [2] 311400 0
Australia
Primary sponsor type
Other Collaborative groups
Name
South Australian Health and Medical Research Institute
Address
South Australian Health and Medical Research Institute
North Terrace, Adelaide SA, 5000, Australia
Country
Australia
Secondary sponsor category [1] 312789 0
University
Name [1] 312789 0
Adelaide Medical School, The University of Adelaide
Address [1] 312789 0
Adelaide Healh and Medical Sciences Building, The University of Adelaide, Adelaide SA 5000
Country [1] 312789 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 310881 0
Central Adelaide Local Health Network HREC
Ethics committee address [1] 310881 0
CALHN HREC
RAH Clinical Trial Centre
Wayfinder 3D460.02
Level 3, Royal Adelaide Hospital
Port Road
ADELAIDE SA 5000
Ethics committee country [1] 310881 0
Australia
Date submitted for ethics approval [1] 310881 0
Approval date [1] 310881 0
13/04/2021
Ethics approval number [1] 310881 0

Summary
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.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 119210 0
Dr Ryan O'Hare Doig
Address 119210 0
Level 7, Neil Sachse Centre for Spinal Cord Research
South Australian Health and Medical Research Institute
North Terrace, Adelaide, SA 5000
Country 119210 0
Australia
Phone 119210 0
+61 8 8128 4744
Fax 119210 0
Email 119210 0
[email protected]
Contact person for public queries
Name 119211 0
Dr Ryan O'Hare Doig
Address 119211 0
Level 7, Neil Sachse Centre for Spinal Cord Research
South Australian Health and Medical Research Institute
North Terrace, Adelaide, SA 5000
Country 119211 0
Australia
Phone 119211 0
+61 8 8128 4744
Fax 119211 0
Email 119211 0
[email protected]
Contact person for scientific queries
Name 119212 0
Dr Ryan O'Hare Doig
Address 119212 0
Level 7, Neil Sachse Centre for Spinal Cord Research
South Australian Health and Medical Research Institute
North Terrace, Adelaide, SA 5000
Country 119212 0
Australia
Phone 119212 0
+61 8 8128 4744
Fax 119212 0
Email 119212 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Individual data of published results only will be available. Other (unpublished) data, such as additional de-identified individual data of primary and/or secondary outcomes may be available upon reasonable request.
When will data be available (start and end dates)?
No data will be available until completion and publication of the full study. Data will then become available 12 months after publication, unless upon reasonable request.
Available to whom?
Available to anyone upon reasonable request.
Available for what types of analyses?
Meta analysis, protocol analysis
How or where can data be obtained?
By emailing the primary investigator. Dr Ryan O'Hare Doig ([email protected])


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.