Spinal Cord Injury Neurorecovery Collaboration (SCINC)

Spinal Cord Injury Neurorecovery Collaboration (SCINC) Master Protocol

SCINC is an adaptive design Master protocol that seeks to determine if there is "sufficient promise" of beneficial effect of treatment combinations to enhance motor recovery in pre-specified strata of people with a spinal cord injury.

Study Overview

• Status: Recruiting
• Conditions: Spinal Cord Injuries
• Intervention / Treatment: Other: Therapeutic Intermittent Hypoxia (TIH) + Exercise Training (ET)

Detailed Description

SCINC utilises an adaptive design with interim analyses to assess whether a given intervention is futile or shows a "signal of benefit" within an appendix-specific study. The SCINC Master Protocol describes trial procedures, data collection, data monitoring, follow-up visits, and safety procedures that will be employed in all study-specific Appendices. The study-specific Appendix is a Bayesian optimised phase IIA trial, operating under the overarching SCINC Master Protocol. The first study-specific appendix is: Restoration of Respiratory and Upper Limb function after cervical spinal cord Injury (RRULI): Therapeutic Intermittent Hypoxia (TIH) + Exercise Training (ET). The RULLI: Appendix 1 (TIH + ET) aims to determine if ET plus TIH in people with chronic tetraplegia is a therapy with sufficient promise to test in a Phase IIb/III trial; considering feasibility, safety and efficacy. As new interventions are put forth, they will be added to the Master Protocol as a new Appendix. This Master Protocol describes trial procedures, data collection, data monitoring, follow-up visits, and safety procedures that will be employed in all study-specific Appendices. Each study-specific Appendix will have a process evaluation protocol.

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Laura Stendell; Phone Number: (+61) 468 862 693; Email: laura.stendell@unimelb.edu.au
• Study Contact Backup: Name: Nicole Sheers, PhD; Email: nsheers@unimelb.edu.au

Study Locations

• Australia
  • Victoria
    • Heidelberg, Victoria, Australia, 3084
      • Recruiting
      • Austin Health
      • Contact: Laura Stendell; Phone Number: (+61) 0468 862 693; Email: laura.stendell@unimelb.edu.au

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

SCINC Inclusion Criteria:

- Person with SCI

SCINC Exclusion Criteria:

- Proven contraindication to intervention

RRULI: Appendix 1 (TIH + ET) study-specific inclusion criteria:

• Adults > 18 years of age
• Able to independently ventilate
• Chronic SCI (>1 years post-injury or impairment onset)
• Tetraplegia (C2-T1 level of injury)
• Evidence of motor incomplete paralysis in the upper limb below the neurological level of injury
• Have a documented management plan for their AD if it occurs.

RRULI: Appendix 1 (TIH + ET) study-specific exclusion criteria:

• Pregnancy
• Medical instability, including current or recent (within the previous 6 weeks) infection or inflammation
• Current or recent (within the previous 6 weeks) pressure ulcers or cutaneous lesions
• Poorly controlled diabetes
• An episode of AD in the previous 6 months that required medical intervention to resolve
• Significant other neurological, psychiatric, pulmonary, cardiovascular, orthopaedic, or oncological conditions.
• Currently taking part in another clinical trial
• Upper limb contracture

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RRULI: Appendix 1; In this first arm of SCINC, adults with chronic tetraplegia will be assigned to the RRULI: Appendix 1 intervention.	Other: Therapeutic Intermittent Hypoxia (TIH) + Exercise Training (ET); TIH in combination with upper limb and respiratory ET. The intervention is predominantly home-based and will be delivered three times per week for six weeks.; Other Names: Therapeutic acute intermittent hypoxia (tAIH); Acute intermittent hypoxia (AIH)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
At an individual participant level, the Phase IIA study has a single, binary, composite primary outcome to determine if there is a 'signal of benefit', measuring effectiveness, no deterioration, safety and acceptability.	The single binary outcome includes the following components: A) Effectiveness - Increase above baseline that is equal or more than the predefined outcome-specific stated thresholds, on at least ONE of the: Action Reach Arm Test (ARAT), Handheld dynamometer (GRIP) Maximal inspiratory pressure (MIP) B) No deterioration - No deterioration below baseline. C) Safety - Incidence of Autonomic Dysreflexia (AD) episodes occurring during the intervention period for each individual participant. D) Acceptability - Rate of participant adherence to intervention sessions. Please refer to the following primary outcomes for details of each of these components.	Baseline and 6-weeks.
A) Effectiveness: Increase above baseline that is equal or more than the predefined outcome-specific stated thresholds, on at least ONE of the: Action Reach Arm Test (ARAT), Handheld dynamometer (GRIP) Maximal inspiratory pressure (MIP)	ARAT: Assesses grasp, grip, pinch and gross movement. A minimal clinically important difference of 5.7 points is accepted in SCI. GRIP: Grip strength will be measured according to a standardised procedure. A threshold of 5.0 kg will be used. MIP: Respiratory muscle strength will be measured according to standard procedures. A threshold of 10cmH20 will be used.	Baseline and 6 week follow-up
B) No deterioration	No deterioration (decline below baseline) that is equal or more than the predefined outcome-specific stated threshold, on ANY of the ARAT, GRIP and MIP.	Baseline and 6 week follow-up
C) Safety - Incidence of Autonomic Dysreflexia (AD) episodes occurring during the intervention period for each individual participant.	Fewer than two AD events that fail to resolve with participants usual, community interventions.	Up to 6 weeks.
D) Acceptability - Rate of participant adherence to the intervention, as assessed by monitoring attendance to treatment sessions..	Adherence with at least 70% of treatment sessions.	Up to 6 weeks.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
9-hole Peg test	A test of upper limb dexterity and function. This test will be undertaken using the dominant hand.	Baseline and 6-weeks.
Pinch grip dynamometer	Pinch strength	Baseline and 6-weeks.
Penn Spasm Frequency Scale	Self-report measure of upper limb spasticity composed of 2-parts: Spasm frequency: scale 0 (no spasm) - 4 (spasms occurring more than 10 times per hour).; Spasm severity: scale 1 (mild) - 3 (severe). A higher score indicates a worse outcome for both components of the scale.	Baseline and 6-weeks.
Capabilities of upper extremity questionnaire	Questionnaire assessing upper limb function. Scored on a 7-point scale representing self-perceived difficulty: 1= "totally limited, can't do at all" 7= "not at all limited" Minimum score = 32 Maximum score = 224 (higher score = greater function)	Baseline and 6 weeks
Sleep quality and Obstructive Sleep Apnoea (OSA) will be assessed using polysomnography (a sleep study)	In the week prior to the intervention period, a home-based overnight polysomnography test will occur in the participants home to assess for OSA.	1 day
Perceived work of breathing	Modified Borg dyspnoea scale. A scale from 0 (no difficulty breathing) - 10 (very, very severe) - where a higher score is a worse outcome.	Baseline and 6-weeks.
Respiratory function will assessed using spirometry.	Respiratory function measurement - physiological. Spirometry is a test of lung function and can measure how much air a person can force out of their lungs in 1 second (FEV1), and in total (forced vital capacity, FVC).	Baseline and 6-weeks.
Maximal expiratory pressure (MEP) and sniff nasal inspiratory pressure (SNIP)	Respiratory muscle strength	Baseline and 6-weeks
Peak cough flow (L/min)	Cough effectiveness	Baseline and 6-weeks
Minute Ventilation (Litres)	Ventilation response measurement - physiological.	Baseline and 6-weeks.
End of tidal breathing oxygen and carbon dioxide saturation.	Ventilation response measurement - physiological.	Baseline and 6-weeks.
Respiratory Rate measured in breaths per minute.	Ventilation response measurement - physiological.	Baseline and 6-weeks.
Tidal volume, measured in litres.	Ventilation response measurement - physiological measure.	Baseline and 6-weeks.
Ventilation response - assessing mouth pressure (measured in cmH20)	Ventilation response measure - physiological.	Baseline and 6-weeks.
Inspiratory time, measured in seconds (s).	Ventilation response measurement - physiological.	Baseline and 6-weeks.
Inspiratory and expiratory flow, measured in Litres per second (L/s).	Ventilation response measurement - physiological.	Baseline and 6-weeks.

Collaborators and Investigators

• Sponsor: University of Melbourne
• Collaborators: University of Florida; University of Sydney; Austin Health; The University of New South Wales; Neuroscience Research Australia; Institute of Breathing and Sleep
• Investigators: Principal Investigator: David Berlowitz, PhD, University of Melbourne

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: February 27, 2025
• First Submitted That Met QC Criteria: March 6, 2025
• First Posted (Actual): March 11, 2025

Study Record Updates

• Last Update Posted (Actual): August 8, 2025
• Last Update Submitted That Met QC Criteria: August 4, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Spinal Cord Diseases; Wounds and Injuries; Spinal Cord Injuries
• Other Study ID Numbers: SCINC_MASTER

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified participant level data will be made available for research purposes upon approval of written requests at completion of the trial.
• IPD Sharing Time Frame: Unending - beginning nine months following publication with no end date.
• IPD Sharing Access Criteria: Proposals to access IPD must be directed to the study-specific principal investigator.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No