Optimizing INITIation of Non-invasive Ventilation in ALS Patients (INITIALS)

Objective: The primary objective in this study is to identify which (pheno)type of ALS patient has the most benefit from NIV in improving quality of life.

Study population: Adult patients with ALS, PLS (Primary Lateral Sclerosis) of PSMA (Progressive Spinal Muscular Atrophy) in the Netherlands. Patients will be included during their first visit to one of the HMV centres in the Netherlands.

Main study parameters/endpoints: The main study parameter is change in Quality of Life (QoL) defined as change in ALS Assessment Questionnaire (ALSAQ-40) in patients with ALS after initiation of NIV.

Design: Multi-centre prospective cohort study consisting of 2 non-randomized cohorts, i.e. ALS patients who start NIV and ALS patients who do not start NIV at the time of inclusion in the present study.

Duration: The total duration of the study: 3,5 years. Inclusion period: 30 months. Follow up time after initiation of NIV: 9 months. Thereafter, 6 months will be used for data analysis.

Setting: Involvement of all (4) HMV centres in the Netherlands (Groningen, Maastricht, Rotterdam, Utrecht).

Procedure: 250 ALS patients will be included. During the first regular visit to the HMV centre patients will be asked to participate in the study. Data will be recorded during regular visits to the HMV centre.

Study Overview

• Status: Recruiting
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Other: Standard care

Detailed Description

First visit:

After informed consent the following data which are gathered as parts of usual care will be recorded in the case report form (CRF):

• Pulmonary function:

  • FVC ( % predicted) upright and supine
  • capillary blood gas analysis, room air (pH, pCO2, HCO3-, pO2)
  • anamnestic questions (Borg scale 0-4)
• Gender
• Age
• Percutaneous Endoscopic Gastrostomy (PEG)/ Percutaneous Radiological Gastrostomy (PRG) tube: yes/no
• Medication
• Weight/ BMI
• Living situation
• Civil status

• The following clinical characteristics from their medical record (from neurologist or rehabilitation specialist):

  • Date of diagnosis
  • Type of ALS at onset
  • ALSFRS-R at the time of diagnosis
  • Pulmonary function at the time of diagnosis
  • Cognitive status (ECAS, ALS-FTD-Q)
  • Medical history

• Validated questionnaires (online):

  • Quality of life questionnaires (SF 36, ALSAQ-40)
  • Respiratory insufficiency questionnaire (SRI)
  • ALS FRS R (patient version)
  • Bulbar symptoms questionnaire (CNS BFS)

After the first visit patients will participate in one of the two cohorts (non-randomized):

• Cohort 1: patients who start NIV in the first two months after the first visit to the HMV
• Cohort 2: patients who do not start NIV in the first two months after the first visit to the HMV.

Cohort 1:

Data will be recorded at the moment of initiation of NIV and 3, 6 and 9 months after initiation. Data will be recorded during regular visits (to the HMV centre or at the patients home).

• Pulmonary function:

  • capillary blood gas, room air (pH, pCO2 (kPa/ mmHg), HCO3- (mmol/l), SaO2 (%))
  • anamnestic questions (Borg scale 0-4)
  • Nocturnal gas exchange by transcutaneous measurement, at the patients home - Mean tcpCO2 (kPa), Maximal tcpCO2 (kPa), mean oxygen saturation (%), lowest oxygen saturation (%)
• Data from NIV equipment (compliance, modus, IPPA, EPAP, freq, mask type)

• Use of NIV

  • hours a day/night
  • In case of no use: why not?
• PEG/ PRG tube: yes/no
• Survival
• Tracheostomy or not
• Weight

• Validated online questionnaires:

  • Quality of life questionnaires (SF 36, ALSAQ-40)
  • Respiratory insufficiency questionnaire (SRI)
  • ALS FRS R (patient version)
  • Bulbar symptoms questionnaire (CNS BFS)
• Nocturnal gas exchange, transcutaneous, at the patients home

Cohort 2:

Data will be recorded every 3 months until initiation of NIV or death or max 1,5 years after the first visit to the HMV.

Data will be recorded during regular visits (to the HMV centre or at the patients home).

• Pulmonary function:

  • Capillary blood gas (pH, pCO2 (kPa/ mmHg), HCO3- (mmol/l), SaO2 (%))
  • anamnestic questions (Borg scale 0-4)
  • Nocturnal gas exchange by transcutaneous measurement, at the patients home - tcpCO2 (kPa), Maximal tcpCO2 (kPa), oxygen saturation (%), lowest oxygen saturation (%)
• PEG/ PRG tube: yes/no
• Survival
• Tracheostomy or not
• Weight
• Cognitive status (from medical record)
• Reason for not starting NIV

• Validated online questionnaires:

  • Quality of life questionnaires (SF 36, ALSAQ-40)
  • Respiratory insufficiency questionnaire (SRI)
  • ALS FRS R (patient version)
  • Bulbar symptoms questionnaire (CNS BFS)
• Nocturnal gas exchange, transcutaneous, at the patients home

If a patient in cohort 2 will start with NIV, the patient will be transferred to cohort 1.

• Study Type: Observational
• Enrollment (Estimated): 250

Contacts and Locations

• Study Contact: Name: Rineke Jaspers Focks, MD; Phone Number: +31534875424; Email: r.jaspersfocks@roessingh.nl
• Study Contact Backup: Name: Peter Wijkstra, MD, PhD; Phone Number: +31503613200; Email: p.j.wijkstra@umcg.nl

Study Locations

• Netherlands
  • Groningen, Netherlands, 9700RB
    • Recruiting
    • University Medical Centre Groningen
    • Contact: Peter wijkstra, MD PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients must be diagnosed with Amyotrophic Lateral Sclerosis (ALS), Progressive Spinal Muscular Atrophy (PSMA) or Primary Lateral Sclerosis (PLS) by a neurologist.

The patients will be included (after signing informed consent) during the first visit to one of the HMV centres in the Netherlands. Patients must to be able to participate and at least 18 years old

Description

Inclusion Criteria:

• Age > 18 years
• Diagnosis of ALS, PLS or PSMA
• Ability to give informed consent.
• Ability to fill in the questionnaires independently or with assistance of a caregiver.

Exclusion Criteria:

• Use of NIV or invasive ventilation (tracheostomy) at time of first visit to a HMV centre.
• Pregnancy

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cohort 1; Patients who start NIV in the first two months after the first visit to the HMV	Other: Standard care; Both groups: standard care+ questionnaires
Cohort 2; Patients who do not start NIV in the first two months after the first visit to the HMV.	Other: Standard care; Both groups: standard care+ questionnaires

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Health related Quality of Life in patients with ALS	Assessed by Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40) Min score: 0 Max score: 160 Higher scores mean a worse outcome	15 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival	Determine the effect of NIV on survival in patients with different ALS phenotypes.	15 months
Overall function	Overall function decline based on the ALS Functional Rating Scale Revised (ALS-FRS-R). Min score: 0 Max score: 48 Higher scores mean a worse outcome	15 months
Forced vital capacity	Pulmonary function based on FVC Min score: 0% Max score: 100% Lower scores mean a worse outcome	15 months
Carbondioxide	Pulmonary function based on carbondioxide pCO2 in capillary bloodgas Min score: 4 kPa Max score: 9 kPa Higher score means a worse outcome	15 months
Anamnestic questions	Pulmonary function based on anamnestic questions, Borg scale Min score: 0 Max score: 40 Higher score means a worse outcome	15 months
Bulbar function	Bulbar function based on questionnaire Center for Neurological Study Bulbar Functional Scale (CNS BFS). Min score: 21 Max score: 105 Higher scores means a worse outcome	15 months
Weight	Weight in kg Min score: 40 Max score 130 Lower scores mean a worse outcome	15 months
General health Quality of Life in patients with severe respiratory insufficiency	Assessed by severe respiratory insufficiency questionnaire (SRI) Min score: 49 Max score: 245 Higher scores mean worse outcome	15 months
General health Quality of Life	Assessed by in Short Form Health Survey (SF-36) Min score: 45 Max score: 198 Higher score means a worse outcome	15 months

Collaborators and Investigators

• Sponsor: University Medical Center Groningen

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2022
• Primary Completion (Estimated): April 1, 2025
• Study Completion (Estimated): October 1, 2025

Study Registration Dates

• First Submitted: July 7, 2021
• First Submitted That Met QC Criteria: August 27, 2021
• First Posted (Actual): September 5, 2021

Study Record Updates

• Last Update Posted (Actual): May 16, 2024
• Last Update Submitted That Met QC Criteria: May 14, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Quality of life; Noninvasive ventilation
• Additional Relevant MeSH Terms: Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Motor Neuron Disease; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: 202000124

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No