Intraspinal Transplantation of Autologous ADRC in ALS Patients (ADIPOSTEM)

Safety and Efficacy of Intraspinal Transplantation of Autologous ADRC in ALS Patients

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).

Study Overview

• Status: Unknown
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Biological: Cell-based therapy of autologous adipose derived regenerative cells transplanted intraspinally and intrathecally in ALS patients

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).

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• Poland
  • Warsaw, Poland, 02-097
    • Medical University of Warsaw

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

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: Autologous ADRC injection	Biological: Cell-based therapy of autologous adipose derived regenerative cells transplanted intraspinally and intrathecally in ALS patients; 3 injections of ADRC: 1 intraspinal and 2 intrathecal

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional progression rate	Delta ALS Functional Rating Scale (ALSFRS-R)/month	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Electrophisiological progression rate	electromyography (EMG)/ Motor unit number index (MUNIX)	3 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Respiratory insufficiency estimation	Forced Vital Capacity (FVC)	3 months

Collaborators and Investigators

• Sponsor: Mossakowski Medical Research Centre Polish Academy of Sciences
• Collaborators: Medical University of Warsaw

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): October 13, 2015
• Primary Completion (Anticipated): October 31, 2020
• Study Completion (Anticipated): October 31, 2022

Study Registration Dates

• First Submitted: September 21, 2017
• First Submitted That Met QC Criteria: September 23, 2017
• First Posted (Actual): September 28, 2017

Study Record Updates

• Last Update Posted (Actual): April 15, 2020
• Last Update Submitted That Met QC Criteria: April 14, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: ALS; ADRC; adipose derived regenerative cells; intraspinal transplantation; mesenchymal cells
• 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: DPO/014/33/09/2015

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