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Amyotrophic Lateral Sclerosis and the Innate Immune System

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ClinicalTrials.gov Identifier: NCT02869048
Recruitment Status : Recruiting
First Posted : August 16, 2016
Last Update Posted : October 6, 2017
Information provided by (Responsible Party):

Study Description
Brief Summary:

Amyotrophic Lateral Sclerosis (ALS) is an aggressive, deadly disease. ALS leads to destruction of the neural pathways which control the conscious movements of the muscles. This destruction leads to muscular dystrophy with increasing difficulties in moving, breathing, swallowing, and speaking. In the last phase of an ALS patient's life it is necessary with respiratory therapy in order to breathe. In average an ALS patient lives 3 years from the time he or she gets the diagnose.

The cause of the disease is still unknown and there is currently no treatment which can stop the progression of the disease. Former clinical studies have indicated that the innate immune system and in particular the complement system plays a significant role in the progression of ALS. The complement system, which is activated in cascades, is part of the innate system but participates in the innate as well as the acquired immune system. Former clinical trials have been characterized by limited knowledge about both the complement system as well as to how it is measured.

Today it is possible to measure directly on the different components of the complement system and to understand its contribution to the overall immune response. It is also possible today to detect defects of the complement system. All these progressions are the foundation for this project which is carried out in close cooperation with one of the world's leading researchers in the complement system, professor Peter Garred from Rigshospitalet.

The aim is to make a national research project about ALS in order to investigate the role of the innate immune system, and especially the complement system, in patients with ALS.

In the long term the hope is, that this will lead the way to a targeted and effective medical treatment to the people affected by this grave disease.

Condition or disease
Amyotrophic Lateral Sclerosis Neurodegenerative Disease Motor Neuron Disease

  Show Detailed Description

Study Design

Study Type : Observational
Estimated Enrollment : 375 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Amyotrophic Lateral Sclerosis and the Innate Immune System
Study Start Date : June 2016
Estimated Primary Completion Date : June 2026
Estimated Study Completion Date : June 2026

Groups and Cohorts

ALS patients
Patients diagnosed with ALS will be included in this group. Blood and spinal fluid samples will be stored in biobank and later analyzed. A subset of this group (20 ALS patients) will give blood and spinal fluid every 6 months during progression of the disease. A subset of 10 will donate a muscle biopsy.
Control group with patients with other neurological disease
Patients referred to hospital with symptoms of acute or chronic headache.
Neurologically healthy control group
Patients having orthopaedic surgery performed in spinal anaesthesia.

Outcome Measures

Primary Outcome Measures :
  1. Complement activity [ Time Frame: 0-10 year ]
    The complement activity (measured by haemolytic capacity, complement-activation potential and specific mediators) in ALS patients and compared with 2 control groups.

Secondary Outcome Measures :
  1. Subcomponents of the complement cascade [ Time Frame: 0-10 years ]
    If increased complement activity is found, the amount of the different subcomponents of the complement cascade are measured and compared with the 2 control groups.

  2. Inactivation of the complement system [ Time Frame: 0-2 years ]
    The effect of inactivation by heat or inhibition of the complement system with anti-complement in the plasma is analyzed by comparing the degree of haemolysis after incubation compared with the test results of the plasma which is not inactivated by heat nor with added anti-complement.

  3. Indirect profiling of inflammatory proteins present in the blood [ Time Frame: 0-10 years ]
    RNA expression profile of the ALS patients compared with the 2 control groups

  4. Cytokines present in the blood [ Time Frame: 0-10 years ]
    The cytokines are measured in ALS patients and compared with the 2 control groups.

  5. Acut phase reactants [ Time Frame: 0-10 years ]
    The acute phase reactants are measured in ALS patients and compared with the 2 control groups.

  6. Complement activity in the neuromuscular junctions of ALS patients. (Clinical trial 4) [ Time Frame: 0-3 years ]
    The amount of complement deposition as well as complement activity in the neuromuscular junctions are described quantitatively as well as qualitatively

  7. Quantitatively and qualitatively description of ALS muscle fibers. [ Time Frame: 0-3 years ]
    The muscle fibres are described quantitatively as well as qualitatively and compared historically collected material of healthy muscle fibers.

  8. Regression analysis [ Time Frame: 0-10 years ]
    The immune response of the ALS patients is analyzed as a function of sex, age, subtype of disease, stage of disease, severity of disease, duration of disease, present smoking, alcohol consumption, present use of medicine (including riluzole). The regression analysis will be compared when possible with the 2 control groups (sex, age, smoking, alcohol consumption, use of medicine).

Biospecimen Retention:   Samples With DNA

Serum, EDTA-plasma, Hirudin-plasma, Heparin-plasma and RNAlater samples (with fullblood) will be kept in biobank as well as analyzed according design and methods of Clinical study 1+2+3.

Spinal liquid sample will also be kept in biobank (Clinical Study 2+3).

10 muscle biopsies from ALS patients will be analyzed (Clinical study 4)

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

ALS group: Patients diagnosed with certain or likely ALS

Neurological control group:

Patients being examined for cronical headache or being referred to hospital to get a lumbar perfusion test performed.

Neurologically healthy control group:

Clinical study 1: Healty employees from Rigshospitalet Clinical study 2: Neurologically healthy patients having planned orthopaedic surgery performed in spinal anaestesia.


Inclusion Criteria:

  • For ALS group:Diagnosed with the diagnose category "certain ALS" or "likely ALS according to the El Escorial rev. diagnose criteria
  • For Neurological control group: Referred to neurological department to be examined for acute or chronic headache or referred to get a lumbar perfusion test performed.

Exclusion Criteria:

  • For all groups (Clinical study 2-3): permanent contraindication for having a lumbar puncture performed
  • For Neurological control group: Known with chronic inflammatory disease or autoimmune disease.
  • For healthy control group (clinical study 1): Known with any disease
  • For healthy control group (clinical study 1): Taking daily medication
  • For Neurologically healthy control group (Clinical study 2): Known with neurological disease
  • For Neurologically healthy control group (Clinical study 2): Known with chronic inflammatory disease or autoimmune disease.
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02869048

Contact: Anne-Lene Kjældgaard, MD akja004@regionh.dk

Dept. of Neurology Aarhus Hospital, Nørrebrogade Recruiting
Aarhus, Denmark, 8000
Contact: Anette Torvin Møller, MD, PhD         
Gildhøj Private Hospital Completed
Brøndby, Denmark, 2605
Dept. of Neurology, Bisbebjerg Hospital Recruiting
Copenhagen NV, Denmark, 2400
Contact: Merete Karlsborg, MD         
Clinic of Neurosurgery, Rigshospitalet Not yet recruiting
Copenhagen Ø, Denmark, 2100
Contact: Marianne Juhler, dr.med, prof         
Clinic of neuroanestesiology, Rigshospitalet Glostrup Recruiting
Copenhagen, Denmark, 2600
Contact: Anne-Lene Kjældgaard, MD         
The Dept. og Neurology, Rigshospitalet Glostrup Recruiting
Glostrup, Denmark, 2600
Contact: Elisabeth Elmo, MD         
Dept. of Neurology, Odense Hospital Recruiting
Odense C, Denmark, 5000
Contact: Matthias Bode, MD         
The dept. of Neurology, Roskilde Hospital Recruiting
Roskilde, Denmark, 4000
Contact: Helle Thagesen, MD         
Sponsors and Collaborators
Rigshospitalet, Denmark
Zealand University Hospital
Bispebjerg Hospital
Aarhus University Hospital
Odense University Hospital
Study Chair: Kirsten Møller, Prof., MD Clinic of Neuroanestesiology, Rigshospitalet, Denmark
Study Chair: Peter Garred, Prof., MD Department of Clinical Immunology
Study Chair: Stephen Wørlich Pedersen, dr.med Dept. of Neurology, Rigshospitalet Glostrup
Study Chair: Karsten Skovgaard Olsen, Dr.med. Clinic of Neuroanaestesiology, Rigshospitalet Glostrup
Study Chair: Anne Øberg Lauritsen, MD Clinic of Neuroanaestesiology, Rigshospitalet Glostrup
Study Chair: Eva Løbner Lund, MD, PhD Dept. of Pathology, Rigshospitalet
Principal Investigator: Anne-Lene Kjældgaard, MD Clinic of Neuroanaestesiology, Rigshospitalet Glostrup
More Information

Conradi, S. Cytotoxic factor in plasma from ALS patients provokes haemolysis of normal erythrocytes. Acta Neurologica Scandinavica, 65: 246-247, 1982
Ronnevi, LO., Conradi, S. and Karlsson, E. Cytotoxic effect of immunoglobulins in Amyotrophic Lateral Sclerosis (ALS). Acta Neurologica Scandinavica, 69: 182-183, 1984
Armitage P BG. Statistical Methods for Medical Researchers. Blackwell1994.

Responsible Party: Anne-Lene Kjældgaard, Ph.d.-student, MD, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier: NCT02869048     History of Changes
Other Study ID Numbers: H-16017145
First Posted: August 16, 2016    Key Record Dates
Last Update Posted: October 6, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Anne-Lene Kjældgaard, Rigshospitalet, Denmark:
Biological Specimen Banks
Innate Immunity
Clinical Study
Complement system proteins
Amyotrophic lateral sclerosis
Neurodegenerative disease
Motor neuron disease

Additional relevant MeSH terms:
Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Neurodegenerative Diseases
Pathologic Processes
Nervous System Diseases
Neuromuscular Diseases
Spinal Cord Diseases
Central Nervous System Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases