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MIG-HD: Multicentric Intracerebral Grafting in Huntington's Disease (MIG-HD)

Primary Purpose

Huntington Disease

Status
Completed
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
graft intracerebral of foetal neurons
Sponsored by
Assistance Publique - Hôpitaux de Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Huntington Disease focused on measuring Huntington, graft, cellular therapy, striatum

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Disease clinically declared since at least 1 year ,UHDRS motor > or =5 TFC > or = 10. CAG > or = 36 Age between 18 and 65 Family and socially integrated subject Informed consent. Exclusion Criteria: Severe intellectual deterioration or neuropsychiatric disorders making the follow-up longitudinal too complicated (score MATTIS < 120). Not-observance of the appointments and the symptomatic treatments in pre-surgical period. Intercurrent disease making a surgical operation impossible. Associated disease having a neurological repercussion, intercurrent cerebral lesion with the IRM. Visceral affection engraves, evolutionary, which brings into play the vital forecast or makes risks for general anaesthesia. Mental Affection likely to disturb adhesion with the protocol, and in particular antecedents of hallucinations spontaneous and/or induced by the drugs; antecedents of serious depression having required repeated hospitalizations; antecedents of repeated suicide attempts. Cerebral morphological anomalies, others that those characteristic of the disease, noted with the IRM or the tomodensitometry. Participation in progress, or stopped since less than three months, with a therapeutic protocol of the Huntington's disease Exclusion Criteria (pre-randomization) TFC < 8 Not-observance of the appointments and the symptomatic treatments in pre-surgical period. Intercurrent disease returning the surgery or impossible immunosuppression. v Subject completely isolated with his family and socially.. UHDRS motor < 5. Positives serologies for HIV1, HIV2, AgP24, HTLV1 et 2, HEPATITE B, HEPATITE C, syphilis Psychiatric disorders being able to compromise the follow-up. Signs other than Huntington with the IRM.

Sites / Locations

  • Hopital Henri Mondor

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

1

2

Arm Description

Early Graft (Early G)

Late Graft (Late G)

Outcomes

Primary Outcome Measures

Motor UHDRS rating scale, at randomization, 20 month after transplant

Secondary Outcome Measures

Neurologic, Cognitive, Neurophysiologic, Psychiatric, MRI and Pet-scan evaluation at randomization, 20 month after and at the end of the protocol

Full Information

First Posted
September 15, 2005
Last Updated
October 12, 2017
Sponsor
Assistance Publique - Hôpitaux de Paris
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1. Study Identification

Unique Protocol Identification Number
NCT00190450
Brief Title
MIG-HD: Multicentric Intracerebral Grafting in Huntington's Disease
Acronym
MIG-HD
Official Title
Multicentric Intracerebral Grafting in Huntington's Disease
Study Type
Interventional

2. Study Status

Record Verification Date
October 2017
Overall Recruitment Status
Completed
Study Start Date
January 2002 (undefined)
Primary Completion Date
December 2013 (Actual)
Study Completion Date
December 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The aim of this study is to assess the clinical benefit of intrastriatal grafting of human cells from the foetal ganglionic eminence in patients with Huntington's disease. The duration of the study will be 52 months. A first group of patients will be grafted at M13-14 (early G group) and a second group of patients will be grafted at M33-34 (late G group). The principal criterion is the comparison of the progression between M12 and M32 of the motor score (TMS) of the UHDRS between grafted patients (early G group) and not yet grafted patients (late G group). An additional evaluation will be performed to compare the progression in individual patients over the 52-month study period. We will thus be able to compare the pre and post-graft TMS progression for all patients.
Detailed Description
The aim of this study is to show the existence of a clinical benefit rising from a substitution of the striatal neurons degenerated among a large cohort of Huntington's patient at early stage by homologous neurons coming from human foetuses, This effect will be estimated, compared with a group of patients not treated at first, on the results of the motor scale of the Unified Huntington Disease Rating Scale (UHDRS, Huntington study group, on 1996). Transplants will be realized in two surgical times to avoid the risk of hurts per-operating, BI-CAUDES, if transplants were realized at single time. The minimal interval between both transplants will be of 2 weeks, so as to let the patient recover of the first general anaesthesia It's a multicentric study of phase II randomised and controlled, with direct individual benefit.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Huntington Disease
Keywords
Huntington, graft, cellular therapy, striatum

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
54 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
Early Graft (Early G)
Arm Title
2
Arm Type
Experimental
Arm Description
Late Graft (Late G)
Intervention Type
Biological
Intervention Name(s)
graft intracerebral of foetal neurons
Intervention Description
graft intracerebral of foetal neurons
Primary Outcome Measure Information:
Title
Motor UHDRS rating scale, at randomization, 20 month after transplant
Time Frame
during de study
Secondary Outcome Measure Information:
Title
Neurologic, Cognitive, Neurophysiologic, Psychiatric, MRI and Pet-scan evaluation at randomization, 20 month after and at the end of the protocol
Time Frame
during the study

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Disease clinically declared since at least 1 year ,UHDRS motor > or =5 TFC > or = 10. CAG > or = 36 Age between 18 and 65 Family and socially integrated subject Informed consent. Exclusion Criteria: Severe intellectual deterioration or neuropsychiatric disorders making the follow-up longitudinal too complicated (score MATTIS < 120). Not-observance of the appointments and the symptomatic treatments in pre-surgical period. Intercurrent disease making a surgical operation impossible. Associated disease having a neurological repercussion, intercurrent cerebral lesion with the IRM. Visceral affection engraves, evolutionary, which brings into play the vital forecast or makes risks for general anaesthesia. Mental Affection likely to disturb adhesion with the protocol, and in particular antecedents of hallucinations spontaneous and/or induced by the drugs; antecedents of serious depression having required repeated hospitalizations; antecedents of repeated suicide attempts. Cerebral morphological anomalies, others that those characteristic of the disease, noted with the IRM or the tomodensitometry. Participation in progress, or stopped since less than three months, with a therapeutic protocol of the Huntington's disease Exclusion Criteria (pre-randomization) TFC < 8 Not-observance of the appointments and the symptomatic treatments in pre-surgical period. Intercurrent disease returning the surgery or impossible immunosuppression. v Subject completely isolated with his family and socially.. UHDRS motor < 5. Positives serologies for HIV1, HIV2, AgP24, HTLV1 et 2, HEPATITE B, HEPATITE C, syphilis Psychiatric disorders being able to compromise the follow-up. Signs other than Huntington with the IRM.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
A-C. BACHOUD-LEVI, MD,PhD
Organizational Affiliation
Assistance Publique - Hôpitaux de Paris
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hopital Henri Mondor
City
Paris
State/Province
Ile de France
ZIP/Postal Code
94000
Country
France

12. IPD Sharing Statement

Citations:
PubMed Identifier
11130527
Citation
Bachoud-Levi AC, Remy P, Nguyen JP, Brugieres P, Lefaucheur JP, Bourdet C, Baudic S, Gaura V, Maison P, Haddad B, Boisse MF, Grandmougin T, Jeny R, Bartolomeo P, Dalla Barba G, Degos JD, Lisovoski F, Ergis AM, Pailhous E, Cesaro P, Hantraye P, Peschanski M. Motor and cognitive improvements in patients with Huntington's disease after neural transplantation. Lancet. 2000 Dec 9;356(9246):1975-9. doi: 10.1016/s0140-6736(00)03310-9.
Results Reference
result
PubMed Identifier
35567614
Citation
Riad R, Lunven M, Titeux H, Cao XN, Hamet Bagnou J, Lemoine L, Montillot J, Sliwinski A, Youssov K, Cleret de Langavant L, Dupoux E, Bachoud-Levi AC. Predicting clinical scores in Huntington's disease: a lightweight speech test. J Neurol. 2022 Sep;269(9):5008-5021. doi: 10.1007/s00415-022-11148-1. Epub 2022 May 14.
Results Reference
derived
PubMed Identifier
32666599
Citation
Bachoud-Levi AC; on behalf the Multicentric Intracerebral Grafting in Huntington's Disease Group. Human Fetal Cell Therapy in Huntington's Disease: A Randomized, Multicenter, Phase II Trial. Mov Disord. 2020 Aug;35(8):1323-1335. doi: 10.1002/mds.28201. Epub 2020 Jul 15.
Results Reference
derived
PubMed Identifier
26714284
Citation
Schramm C, Katsahian S, Youssov K, Demonet JF, Krystkowiak P, Supiot F, Verny C, Cleret de Langavant L, Bachoud-Levi AC; European Huntington's Disease Initiative Study Group and the Multicentre Intracerebral Grafting in Huntington's Disease Group. How to Capitalize on the Retest Effect in Future Trials on Huntington's Disease. PLoS One. 2015 Dec 29;10(12):e0145842. doi: 10.1371/journal.pone.0145842. eCollection 2015.
Results Reference
derived
PubMed Identifier
18334537
Citation
Teichmann M, Gaura V, Demonet JF, Supiot F, Delliaux M, Verny C, Renou P, Remy P, Bachoud-Levi AC. Language processing within the striatum: evidence from a PET correlation study in Huntington's disease. Brain. 2008 Apr;131(Pt 4):1046-56. doi: 10.1093/brain/awn036. Epub 2008 Mar 11.
Results Reference
derived
Links:
URL
http://www.hdnetwork.org/
Description
Huntington french speaking network website

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MIG-HD: Multicentric Intracerebral Grafting in Huntington's Disease

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