Clinical trial NCT03296501: Intraspinal Transplantation of Autologous ADRC in ALS Patients
Official title: Safety and Efficacy of Intraspinal Transplantation of Autologous ADRC in ALS Patients
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Amyotrophic Lateral Sclerosis
Keywords: ALS
ADRC
adipose derived regenerative cells
intraspinal transplantation
mesenchymal cells
Lead sponsor: Mossakowski Medical Research Centre Polish Academy of Sciences
Sponsor class: OTHER
Collaborators: name: Medical University of Warsaw
First posted: 2017-09-28
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The goal of our nonrandomized, open label study is to investigate the safety and efficacy of autologous adipose derived mesenchymal regenerative cells (ADRC) transplantation into the individuals with diagnosed amyotrophic lateral sclerosis (ALS). All enrolled patients will have a documented at least 3-months clinical and electrophisiological observation of ALS disease course prior to study enrollment. Each patient will recive 3 injections of ADRC every 3 months: an intraspinal injection followed by 2 subsequent intrathecal infusions. Safety, adverse events and efficacy will be confirmed by clinical, elecrophisiological ( EMG, MUNIX), neuroimmaging and spirometry together with functional (ALSFRS-R) and objective motor assesment (MRC and dynamometer).

Detailed description: Amyotrophic Lateral Sclerosis (ALS) is an incurable disease of unknown etiology that in a short time leads to significant impairment of motor functions and death. The frequency of ALS is 4-8/100 000. Mostly it affects people between 40 and 70 years old, but it can occur at a younger age. Since the symptom onset is most frequently in the fifth or sixth decade, ALS is a huge economic burden for the society. There are many studies conducted to treat the disease and prevent it, but currently the medicine offers only one drug that can slow the appearance of disease symptoms but could not stop the progression. Yet, improvements in medical management, including nutrition and breathing, regularly increase patient survival - 50% of affected patients live at least 3 or more years after diagnosis; 20% live 5 years or more; and up to 10% will survive more than 10 years. The stem-cell-based therapies could be therefore a new waited strategy for ALS clinical treatment.

Since the clinical course of ALS may vary substantially between patients, we are planning to qualify them with a primarily established clinical course based on a detailed anamnesis and clinical assessment. The goal of our nonrandomized, open label study is to investigate the safety and efficacy of autologous adipose derived mesenchymal regenerative cells (ADRC) transplantation into the individuals with diagnosed amyotrophic lateral sclerosis. In order to select a group of 30 ALS patients for the ADRC treatment, approximately 50 ALS patients will be examined. All patients enrolled will have a documented at least 3-months clinical and electrophisiological observation of ALS disease course prior to study enrollment. Each patient will recive 3 injections of ADRC every 3 months: an intraspinal injection followed by 2 subsequent intrathecal infusions. Safety, adverse events and efficacy will be confirmed by clinical, elecrophisiological ( EMG, MUNIX), neuroimmaging and spirometry together with functional (ALSFRS-R) and objective motor assesment (MRC and dynamometer).

Eligibility criteria: Inclusion Criteria:

* clinically definite or probable ALS according to El Escorial criteria
* life expectancy of more than 1 year
* INR ≤2 before liposuction
* lack of treatment with immune-suppressants and/or corticosteroids within min. 20 days prior to recruitment
* constant riluzole treatment (50 mg/bid) throughout the study period
* compliance with treatment regimen e.g. will and possibility to attend check-up visits
* Polish citizens

Exclusion Criteria:

* primary haematological disease, including hypercoagulable states
* Presence of comorbidity that would stand in the way of neurosurgical treatment-
* previous history of a spinal-cord surgery at the clinically affected level
* previous/current history of neoplasm or comorbidity that could impact upon patient's survival
* PEG
* pregnancy /lactation
* noninvasive/invasive mechanical ventilation at time of recruitment
* alcohol abuse, cocaine amphetamine, etc.

Primary outcomes:
measure: Functional progression rate
timeFrame: 3 months
Secondary outcomes:
measure: Electrophisiological progression rate
timeFrame: 3 months
Other outcomes:
measure: Respiratory insufficiency estimation
timeFrame: 3 months
Locations:
city: Warsaw
country: Poland
facility: Medical University of Warsaw
Study officials:
References:
citation: Kuzma-Kozakiewicz M, Marchel A, Kaminska A, Gawel M, Sznajder J, Figiel-Dabrowska A, Nowak A, Maj E, Krzesniak NE, Noszczyk BH, Domanska-Janik K, Sarnowska A. Intraspinal Transplantation of the Adipose Tissue-Derived Regenerative Cells in Amyotrophic Lateral Sclerosis in Accordance with the Current Experts' Recommendations: Choosing Optimal Monitoring Tools. Stem Cells Int. 2018 Aug 12;2018:4392017. doi: 10.1155/2018/4392017. eCollection 2018.