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

• ClinicalTrials.gov Identifier: NCT00190450
• Recruitment Status: Completed
• First Posted: September 19, 2005
• Last Update Posted: October 13, 2017
• Sponsor: Assistance Publique - Hôpitaux de Paris
• Information provided by (Responsible Party): Assistance Publique - Hôpitaux de Paris

Tracking Information

• First Submitted Date: September 15, 2005
• First Posted Date: September 19, 2005
• Last Update Posted Date: October 13, 2017
• Study Start Date: January 2002
• Actual Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: October 6, 2017): Motor UHDRS rating scale, at randomization, 20 month after transplant [ Time Frame: during de study ]
• Original Primary Outcome Measures (submitted: September 15, 2005): Motor UHDRS rating scale, at randomization, 20 month after and at the end of the protocol
• Current Secondary Outcome Measures (submitted: October 6, 2017): 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 ]
• Original Secondary Outcome Measures (submitted: September 15, 2005): Neurologic, Cognitive, Neurophysiologic, Psychiatric, MRI and Pet-scan evaluation at randomization, 20 month after and at the end of the protocol
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: MIG-HD: Multicentric Intracerebral Grafting in Huntington's Disease
• Official Title: Multicentric Intracerebral Grafting in Huntington's Disease
• 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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Huntington Disease

Intervention

Biological: graft intracerebral of foetal neurons

graft intracerebral of foetal neurons

Study Arms

• Experimental: 1
  Early Graft (Early G)
  Intervention: Biological: graft intracerebral of foetal neurons
• Experimental: 2
  Late Graft (Late G)
  Intervention: Biological: graft intracerebral of foetal neurons

Publications *

• 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.
• 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.
• 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.
• 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 6, 2017): 54
• Original Enrollment (submitted: September 15, 2005): 60
• Actual Study Completion Date: December 2013
• Actual Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France

Administrative Information

• NCT Number: NCT00190450
• Other Study ID Numbers: P 001106
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Assistance Publique - Hôpitaux de Paris
• Original Responsible Party: Not Provided
• Current Study Sponsor: Assistance Publique - Hôpitaux de Paris
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: A-C. BACHOUD-LEVI, MD,PhD; Assistance Publique - Hôpitaux de Paris

• PRS Account: Assistance Publique - Hôpitaux de Paris
• Verification Date: October 2017