## Protocol Section
### Identification Module
**NCT ID:** NCT06431139

**Acronym:** INSPIRE

**Brief Title:** Intensive Physical Exercise Versus Standard Exercise During Rehabilitation of Patients With Traumatic Brain Injury

**Official Title:** Intensive Physical Exercise Versus Standard Exercise During Rehabilitation of Patients With Traumatic Brain Injury - a Randomised Pilot and Feasibility Trial

#### Organization Study ID Info
**ID:** H-24001505
#### Organization
**Class:** OTHER
**Full Name:** Rigshospitalet, Denmark
### Status Module
#### Completion Date
**Date:** 2026-01-31

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-28

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-24

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2025-10-31

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-07-01

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-28
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-07
**Study First Submit QC Date:** 2024-05-24
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Christian Riberholt

#### Responsible Party

**Investigator Affiliation:** Rigshospitalet, Denmark

**Investigator Full Name:** Christian Riberholt

**Investigator Title:** Head of therapy and senior researcher, PT, MR, PhD

**Type:** SPONSOR_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** The aim of this randomised multicentre clinical feasibility and pilot trial is to test if a sit-to-stand trial protocol is feasible regarding the increased intensity, trial recruitment, and completion of outcome data in patients with moderate to severe traumatic brain injury during the rehabilitation phase. For the trial to be feasible, all outcomes must be achieved.

The primary hypothesis is that it is feasible to progressively increase the number of repetitions of sit-to-stand exercises in patients with moderate to severe traumatic brain injury admitted to a rehabilitation department during the intervention period.

Furthermore, the investigators hypothesize that the increased number of repetitions will increase the participant's functional capabilities regarding sit-to-stand and walking, decrease resting heart rate, blood pressure, and metabolism, reduce inflammatory and brain injury biomarkers, and improve the cognitive performance.

**Detailed Description:** This is a randomised multicentre clinical feasibility and pilot trial, where assessors and statisticians will be blinded. Forty-four participants with moderate to severe traumatic brain injury will be randomised to INSPIRE versus standard care as soon as they are able to understand and execute simple commands twice during one day. Participants in the INSPIRE group will undergo two weeks of intensive sit-to-stand exercise using an algorithm to increase the intensity daily. The trial uses predefined dose-limiting events to reduce training intensity in participants experiencing exercise-related adverse events that limit other daily activities and rehabilitation (e.g. muscle soreness and pain). Overall feasibility will be assessed by determining the inclusion rate, exercise completion rate, and completion of the Glasgow Outcome Scale - Extended. As exploratory clinical outcomes, the investigators will assess serious adverse events and adverse events not considered serious, physical function, cardiovascular and metabolic health, fatigue, and cognitive function.

### Conditions Module

**Conditions:**

- Traumatic Brain Injury

**Keywords:**

- Traumatic brain injury

- Intensive exercise

- Rehabilitation

- Randomised trial

- Feasibility

- Pilot

- Sit-to-stand exercise

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** SINGLE

**Masking Description:** The trial will use assessors blinded to the allocation and in charge of testing the following outcomes: 30 seconds chair stand test, 10-meter walk test, 6-minute walking test, and the Montreal Cognitive Assessment Scoring (MoCA) Two statisticians that will perform the statistical analysis are blinded to the allocation

**Who Masked:**

- OUTCOMES_ASSESSOR

**Primary Purpose:** OTHER

#### Enrollment Info

**Count:** 44

**Type:** ESTIMATED

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Intervention group. Daily intensive sit-to-stand exercises following a described algorithm and utilising motor-relearning principles of feedback to increase the participant's motivation. This exercise is an addition to standard care.

**Intervention Names:**

- Other: INSPIRE intervention protocol

**Label:** INSPIRE group

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** Treatment in this group will be standard care interventions performed at the rehabilitation department.

**Label:** Standard care group

**Type:** NO_INTERVENTION

### Interventions

#### Intervention 1

**Arm Group Labels:**

- INSPIRE group

**Description:** 2-week training program with daily sit-to-stand exercises. Each working day the participant's goals will be adjusted, until exercising a minimum of 100 repetitions using an exercise progression table. When participants complete one level, they will progress to the next level the following day. Participants who do not reach the goals at level one will continue to strive to reach the 100 repetitions. The number of repetitions can be split and performed throughout the day. As the participants' capacity for doing the exercises increases, so will the number of repetitions within each bout of sit-to-stand. Participants are allowed to do the number of repetitions from a higher exercise level if they can and will continue by progressing from that level on the next day. The repetitions will be done from a height that makes it possible to accomplish the sit-to-stand movement. Therefore, the height of the sitting surface will be adjusted according to the participant's abilities.

**Name:** INSPIRE intervention protocol

**Type:** OTHER

### Outcomes Module

#### Other Outcomes

**Description:** Examples of this could be fatigue or muscle pain that limits the participant in other activities of daily living and thereby reduces their amount of other rehabilitation services during the day

**Measure:** Dose-limiting events

**Time Frame:** during the intervention, 72-hours after end of intervention

**Description:** The scale is a global scale evaluating the independent function after traumatic brain injury.

**Measure:** Glasgow Outcome Scale - Extended

**Time Frame:** at discharge, 6 months, 1 year

**Description:** The total number of sit-to-stands in each group will be measured using an activity monitor placed on the participant's sternum and hip (Sens motion®, Copenhagen, Denmark)

**Measure:** Number of sit-to-stand exercises in each group during the intervention period (continuous outcome)

**Time Frame:** during the intervention

**Description:** The test is administered using a stopwatch and a chair. The participant is instructed to do sit-to-stand movements for 30 seconds. Time begins when the participant initiates the movement.

**Measure:** Number of sit-to-stand exercises during the 30-second chair stand test (continuous outcome)

**Time Frame:** Baseline, 1 day after the intervention

**Description:** Walkers are defined by the ability to walk at any pace, with any walking aid, over minimum 50 meters independently (i.e. independent from physical assistance).

**Measure:** Walkers and non-walker (dichotomous outcome)

**Time Frame:** Baseline, 1 day after the intervention

**Description:** The walkers in each group will undergo a 10-meter walk test to assess walking speed

**Measure:** 10-meter walk test (continuous outcome)

**Time Frame:** Baseline, 1 day after the intervention

**Description:** The walkers in each group will undergo a 6-minute walking test to assess and endurance

**Measure:** 6-minute walking test (continuous outcome)

**Time Frame:** Baseline, 1 day after the intervention

**Description:** Resting blood pressure will be measured on both arms for 5 minutes continuously before the first training session (8 am) using photoplethysmography to measure beat-to-beat blood pressure non-invasively.

**Measure:** Resting blood pressure

**Time Frame:** Baseline, 1 day after the intervention

**Description:** An ordinary electrocardiogram available at the respective departments will be used to measure resting heart rate.

**Measure:** Resting heart rate

**Time Frame:** Baseline, 1 day after the intervention

**Description:** The blood samples will be analysed for high-sensitivity C-reactive protein, neutrophil-to-lymphocyte ratio, HbA1c, blood glucose, c-peptide insulin, blood lipids, inflammatory biomarkers, neuronal cell injury biomarkers, astroglia cell injury biomarkers, and axonal injury biomarkers. Finally, biomarkers associated with subacute/chronic traumatic brain injury phase will be analysed.

**Measure:** Blood samples

**Time Frame:** Baseline, 1 day after the intervention

**Description:** The MoCA is a short cognitive questionnaire designed to test for mild cognitive impairments.

**Measure:** The Montreal Cognitive Assessment (MoCA)

**Time Frame:** Baseline, 1 day after the intervention, 6 months, 1 year

**Description:** The Fatigue Severity Scale examines the severity of fatigue with a 9-item scale, and how it can affect a person's daily lifestyle when they have a chronic disease/disorder.

**Measure:** Fatigue severity scale (FSS)

**Time Frame:** Baseline, 1 day after the intervention, 6 months, 1 year

#### Primary Outcomes

**Description:** The difference in the number of sit-to-stand performed in the INSPIRE group compared to the control group using linear regression during the two-week intervention period.

**Measure:** Number of sit-to-stand

**Time Frame:** during the intervention

#### Secondary Outcomes

**Description:** Of all eligible patients, at least 76% (95% CI 63% to 86%, 1-sample proportions test with continuity correction) must consent (by themselves or by proxy) to inclusion in the trial, corresponding to 44/58 eligible patients included

**Measure:** The number of participants included in the trial

**Time Frame:** 1,5 years

**Description:** The number of participants completing the Glasgow Outcome Scale extended at six months and one year must be above 89% (95% CI 76% to 96%), corresponding to 40/44 participants.

**Measure:** Participants completing GOSE

**Time Frame:** 6 months, 1 year

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Moderate to severe traumatic brain injury with Glasgow Coma Score \<13 within the first 24 hours (ICD10, DS06)
* Admitted for rehabilitation at the Department of Brain and Spinal Cord Injury, Division of Brain Injury, Rigshospitalet, the Regional Hospital, Hammel Neurocentre or the Acquired Brain Injury Rehabilitation Centre, Alfred Hospital
* 18 years old or older
* Patients (or next of kin) should be able to understand written and spoken Danish or English to consent to participation in the trial validly
* Specifically for Australian participants: eligibility for Medicare

Exclusion Criteria:

* Unstable fractures of the lower extremities
* Amputation of lower extremity
* Spinal cord injury
* Total paralysis of both lower extremities
* Agitated or combative behaviour
* Diagnosed with a progressive neurological disorder (e.g. Alzheimer's, Parkinson's disease, multiple sclerosis) prior to traumatic brain injury, as it could potentially interfere with serum biomarker levels
* Previous structural brain injury (e.g. stroke or brain surgery)
* No valid consent from the participant or next of kin

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** yasemin.ronahi.kuecuek@regionh.dk

**Name:** Yasemin Ronahi Kücük, M.D

**Phone:** +4527841237

**Role:** CONTACT

**Contact 2:**

**Email:** christian.gunge.riberholt@regionh.dk

**Name:** Christian G Riberholt, PT, MR, PhD

**Role:** CONTACT

#### Overall Officials

**Official 1:**

**Affiliation:** Dept. of Brain and Spinal Cord Injury, Division of Brain Injury, Copenhagen University Hospital - Rigshospitalet

**Name:** Christian G Riberholt, PT, MR, PhD

**Role:** STUDY_DIRECTOR

**Official 2:**

**Affiliation:** Dept. of Brain and Spinal Cord Injury, Division of Brain Injury, Copenhagen University Hospital - Rigshospitalet

**Name:** Christina G Kruuse, Professor

**Role:** STUDY_DIRECTOR

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000001927

- Term: Brain Diseases

- ID: D000002493

- Term: Central Nervous System Diseases

- ID: D000009422

- Term: Nervous System Diseases

- ID: D000006259

- Term: Craniocerebral Trauma

- ID: D000020196

- Term: Trauma, Nervous System

### Condition Browse Module - Browse Branches

- Abbrev: BC10

- Name: Nervous System Diseases

- Abbrev: BC26

- Name: Wounds and Injuries

- Abbrev: All

- Name: All Conditions

### Condition Browse Module - Browse Leaves

- ID: M5207

- Name: Brain Injuries

- Relevance: HIGH

- As Found: Brain Injury

- ID: M628

- Name: Brain Injuries, Traumatic

- Relevance: HIGH

- As Found: Traumatic Brain Injury

- ID: M17685

- Name: Wounds and Injuries

- Relevance: HIGH

- As Found: Injury

- ID: M5204

- Name: Brain Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M5742

- Name: Central Nervous System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M9349

- Name: Craniocerebral Trauma

- Relevance: LOW

- As Found: Unknown

- ID: M22023

- Name: Trauma, Nervous System

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000001930

- Term: Brain Injuries

- ID: D000070642

- Term: Brain Injuries, Traumatic

- ID: D000014947

- Term: Wounds and Injuries

### Misc Info Module

- Version Holder: 2024-05-31
