Autologous Hematopoietic Stem Cell Transplantation for Neurological Damage Associated With Hereditary Homocysteine Remethylation Disorders

NCT07757685 | Not Yet Recruiting DMC

• 1 other identifier: IIT2026053
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 2

Brief Summary

This study aims to evaluate the safety, feasibility, and preliminary efficacy of autologous hematopoietic stem cell transplantation (ASCT) in the treatment of neurological damage associated with hereditary homocysteine remethylation disorders. Meanwhile, peripheral blood, cerebrospinal fluid, and related clinical samples will be prospectively collected before and after transplantation to dynamically monitor changes in immune reconstitution and neuroinflammatory biomarkers. The study intends to explore the impact of immune system resetting on disease progression and central nervous system immune microenvironment, providing evidence for subsequent precise patient stratification and optimized therapeutic strategies.

Conditions

Hereditary Homocysteine Remethylation Disorder

Outcome Measures

Primary Outcomes (1)

• Primary Endpoint: Incidence of adverse events within 100 days post ASCT

  100 days post ASCT

Secondary Outcomes (9)

• Success rate of autologous hematopoietic stem cell collection

  Within 3 days after initiation of stem cell collection

• Time to neutrophil engraftment

  28 days post ASCT

• Time to platelet engraftment

  1 year post ASCT

• 1-year overall survival post ASCT

  1-year post ASCT

• Changes in neurological functional scores

  from baseline to 1 year after ASCT

Study Arms (1)

Patients comprehensively diagnosed with hereditary homocysteine remethylation disorders with neurolo

EXPERIMENTAL

Other: Autologous Hematopoietic Stem Cell Transplantation

Interventions

Autologous Hematopoietic Stem Cell Transplantation OTHER

ASCT Regimen 1. Autologous hematopoietic stem cell collection Mobilization with chemotherapy plus cytokines: * Cyclophosphamide: 30 mg/kg/d, administered intravenously for 2 consecutive days. * G-CSF: 5-10 μg/kg/d subcutaneous injection for 5 consecutive days. Collection target: CD34+ cells ≥ 2×10⁶/kg; repeat leukapheresis permitted to meet target dose. 2. Conditioning Regimen: * Thiotepa: 5 mg/kg/d Day -7 * Fludarabine: 5 mg/kg/d Days -6 to -2 (5 total days) * Rituximab: 375 mg/m² Day -1 3. Stem cell infusion: Day 0 Infusion dose: ≥ 2×10⁶ CD34+ cells/kg

Patients comprehensively diagnosed with hereditary homocysteine remethylation disorders with neurolo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Aged 18 to 55 years, regardless of gender.
• Comprehensive clinical, biochemical, and genetic diagnosis of hereditary homocysteine remethylation disorders.
• Evidence of neurological involvement, including but not limited to gait disturbance, balance impairment, cognitive dysfunction, cerebral white matter lesions.
• Prior standardized metabolic therapy (folic acid, vitamin B12, betaine) with suboptimal clinical response.
• Persistent severe metabolic abnormality, i.e., sustained elevated homocysteine (\>50 umol/L).
• Multidisciplinary consensus confirming lack of effective alternative therapies and ongoing risk of disease progression.
• Voluntary participation, signed informed consent, adequate treatment adherence, and willingness to complete follow-up assessments.

You may not qualify if:

• Prior hematopoietic stem cell transplantation or other cell transplantation.
• Severe dysfunction of critical organs (heart, lung, liver, kidney) deemed incompatible with study treatment by investigators.
• Active, uncontrolled infection.
• Active tuberculosis, hepatitis B, hepatitis C, HIV infection, or other infectious diseases judged inappropriate for enrollment by investigators.
• Active malignancy or prior malignant history that may confound safety and efficacy evaluations.
• Severe underlying comorbidities likely to interfere with study treatment or outcome assessment.
• Severe psychiatric disorder or cognitive impairment with poor adherence precluding completion of treatment and follow-up.
• Pregnant or lactating females, or participants unwilling to use effective contraception throughout the study period.
• Severe hypersensitivity to any study-related medication or intervention.
• Participation in other interventional clinical trials within the past 4 weeks or ongoing observation period of another clinical trial.
• No documented disease progression within the preceding 12 months.
• Minimal neurological symptoms with no meaningful impact on activities of daily living and low short-term progression risk per investigator assessment.
• Established standard therapies proven to alter natural disease history with stable disease and satisfactory therapeutic response.
• End-stage disease with extensive irreversible neurological impairment (severe motor/cognitive failure or multi-organ dysfunction) with minimal expected therapeutic benefit.
• Any other conditions deemed unsuitable for study participation by investigators.

Sponsors & Collaborators

• Institute of Hematology & Blood Diseases Hospital, China: lead

Study Sites (2)

Institute of Hematology & Blood Diseases Hospital, China

Tianjin, Tianjin Municipality, 300020, China

Location

General Hospital of Tianjin Medical University

Tianjin, Tianjin Municipality, 300070, China

Location

Central Study Contacts

Jiang erlie

CONTACT

15122538106; jiangerlie@ihcams.ac.cn

cao yigeng

CONTACT

18622477066; caoyigeng@ihcams.ac.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 21, 2026
• First Posted: August 11, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): July 31, 2030
• Study Completion (Estimated): July 31, 2030
• Last Updated: August 11, 2026

Record last verified: 2026-08

Locations

CN (2)