Retrospective Study on the Safety and Therapeutic/Improvement Effects of Intravenous Administration of SHED-CM for ALS (SHED-CAH2023)

Retrospective Study on the Safety and Therapeutic/Improvement Effects of Intravenous Administration of SHED-CM for ALS

In this study, we will retrospectively evaluate the safety and efficacy of administering SHED-CM for the treatment of ALS.

Study Overview

• Status: Completed
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Biological: The study drug is SHED-CM manufactured by U-Factor

Detailed Description

Amyotrophic Lateral Sclerosis (ALS) is a progressive and irreversible neurodegenerative disease with limited treatment options. Advances in regenerative medicine have opened new avenues for therapeutic interventions. This retrospective cohort study evaluated the safety and efficacy of stem cells from human exfoliated deciduous teeth-conditioned media (SHED-CM) in 24 patients with ALS treated at a single facility between January 1, 2022, and November 30, 2023. Safety assessments included adverse events, vital signs, and laboratory test changes before and after administration, whereas efficacy was measured using the ALS Functional Rating Scale-Revised (ALSFRS-R), grip strength, and forced vital capacity. while ALSFRS-R scores typically decline over time, the progression rate in this cohort was slower, suggesting a potential delay in disease progression. Alternatively, improvements in muscle strength and mobility were observed in some patients. Although adverse events were reported in only 3% of cases (no serious allergic reactions), the treatment-induced changes in vital signs and laboratory results were not clinically significant. The SHED-CM treatment appears to be a safe and potentially effective therapeutic option for patients with ALS. Further research is needed to optimize the SHED-CM treatment; however, this study lays the groundwork for future exploration of regenerative therapies for ALS.

• Study Type: Observational
• Enrollment (Actual): 24

Contacts and Locations

Study Locations

• Japan
  • Tokyo
    • Chiyoda, Tokyo, Japan, 102-0085
      • Hitonowa Medical

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Amyotrophic Lateral Sclerosis

Description

Inclusion Criteria:

• patients who visited our clinic between January 1, 2022 and November 30, 2023 and have been diagnosed with ALS
• male and female patients aged between 16 and 90 years old
• ALSFRS-R score of 12 or more at the time of initial visit

Exclusion Criteria:

• Patients who have a tracheostomy at the time of visit.
• Patients who have expressed their refusal to participate in this study.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Receiving the study drug; Patients diagnosed with ALS who visited our hospital and were administered SHED-CM between January 1, 2022, and November 30, 2023.	Biological: The study drug is SHED-CM manufactured by U-Factor; Patients diagnosed with ALS were administered SHED-CM

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All Adverse Events	This measure will check the total number of adverse events (AEs) reported during the study, categorized by CTCAE Ver 5.0 .	after the treatment
Number of Clinically Significant Changes in Laboratory Test Results	This measure will track the number of events where clinically significant abnormalities are detected in laboratory test parameters, including blood count, biochemistry, and coagulation function tests. Changes from baseline to after the 4th treatment session will be evaluated based on predefined clinical thresholds.	Baseline (pre-treatment) and after 4th treatment
Number of Clinically Significant Changes in Vital Signs	This measure will evaluate the number of events where clinically significant changes in vital signs occur. Parameters include systolic blood pressure, diastolic blood pressure, pulse rate, body temperature, and SpO2. Each event will be assessed at two time points: immediately after treatment and after the 4th treatment session, comparing values to baseline.	Baseline (pre-treatment), post-treatment, and after 4th treatment
Safety assessment during the study period: Adverse events - Self- and other findings	Medical examination, subjective findings, Other findings	after the treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy assessment: Changes in Amyotrophic Lateral Sclerosis Functional Rating Scale Revised version	The revised ALS Functional Rating Scale in ALS Patients. This scale is scored from 0 to 48, the higher the score the better.	Change from baseline at 16 weeks
Efficacy assessment: Changes in %FVC	% forced vital capacity in percent	Change from baseline at 16 weeks
Efficacy assessment: Changes in grip strength	grip strength in kilograms	Change from baseline at 16 weeks

Collaborators and Investigators

• Sponsor: Hitonowa Medical

Publications and helpful links

General Publications

• Oki R, Izumi Y, Fujita K, Miyamoto R, Nodera H, Sato Y, Sakaguchi S, Nokihara H, Kanai K, Tsunemi T, Hattori N, Hatanaka Y, Sonoo M, Atsuta N, Sobue G, Shimizu T, Shibuya K, Ikeda K, Kano O, Nishinaka K, Kojima Y, Oda M, Komai K, Kikuchi H, Kohara N, Urushitani M, Nakayama Y, Ito H, Nagai M, Nishiyama K, Kuzume D, Shimohama S, Shimohata T, Abe K, Ishihara T, Onodera O, Isose S, Araki N, Morita M, Noda K, Toda T, Maruyama H, Furuya H, Teramukai S, Kagimura T, Noma K, Yanagawa H, Kuwabara S, Kaji R; Japan Early-Stage Trial of Ultrahigh-Dose Methylcobalamin for ALS (JETALS) Collaborators. Efficacy and Safety of Ultrahigh-Dose Methylcobalamin in Early-Stage Amyotrophic Lateral Sclerosis: A Randomized Clinical Trial. JAMA Neurol. 2022 Jun 1;79(6):575-583. doi: 10.1001/jamaneurol.2022.0901.

Helpful Links

• We referenced this paper because of the Phase III trial in ALS.

Study record dates

Study Major Dates

• Study Start (Actual): December 25, 2023
• Primary Completion (Actual): July 1, 2024
• Study Completion (Actual): July 1, 2024

Study Registration Dates

• First Submitted: July 18, 2024
• First Submitted That Met QC Criteria: September 19, 2024
• First Posted (Actual): September 23, 2024

Study Record Updates

• Last Update Posted (Actual): September 23, 2024
• Last Update Submitted That Met QC Criteria: September 19, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: Safety; Stem Cells; Therapy; Conditioned Medium; Regenerative Medicine; ALS - Amyotrophic Lateral Sclerosis
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: SHED-CM-ALS-H-2023

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: This was a retrospective cohort study including patients diagnosed with ALS who visited our hospital between January 1, 2022, and November 30, 2023. We enrolled pa-tients with ALS who received SHED-CM within this period, had a score of 12 or higher on the ALS Functional Rating Scale-Revised (ALSFRS-R), and did not undergo trache-ostomy. All administered data were evaluated for safety. Several patients experienced difficulties presenting to the hospital due to the progression of their ALS; therefore, we evaluated the efficacy of the drug from the first to the 12th dose, which were adminis-tered consecutively, and for which all patients presented to the hospital.
• IPD Sharing Time Frame: The original data presented in the study are openly available without restrictions.
• IPD Sharing Access Criteria: The original data presented in the study are openly available in FigShare at 10.6084/m9.figshare.26201615.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; CSR

Drug and device information, study documents

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