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A double-blind, randomized, cross-over, placebo-controlled, pilot trial with Sativex in Huntington’s disease

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Abstract

Huntington’s disease (HD) is a neurodegenerative disease for which there is no curative treatment available. Given that the endocannabinoid system is involved in the pathogenesis of HD mouse models, stimulation of specific targets within this signaling system has been investigated as a promising therapeutic agent in HD. We conducted a double-blind, randomized, placebo-controlled, cross-over pilot clinical trial with Sativex®, a botanical extract with an equimolecular combination of delta-9-tetrahydrocannabinol and cannabidiol. Both Sativex® and placebo were dispensed as an oral spray, to be administered up to 12 sprays/day for 12 weeks. The primary objective was safety, assessed by the absence of more severe adverse events (SAE) and no greater deterioration of motor, cognitive, behavioral and functional scales during the phase of active treatment. Secondary objectives were clinical improvement of Unified Huntington Disease Rating Scale scores. Twenty-six patients were randomized and 24 completed the trial. After ruling-out period and sequence effects, safety and tolerability were confirmed. No differences on motor (p = 0.286), cognitive (p = 0.824), behavioral (p = 1.0) and functional (p = 0.581) scores were detected during treatment with Sativex® as compared to placebo. No significant molecular effects were detected on the biomarker analysis. Sativex® is safe and well tolerated in patients with HD, with no SAE or clinical worsening. No significant symptomatic effects were detected at the prescribed dosage and for a 12-week period. Also, no significant molecular changes were observed on the biomarkers. Future study designs should consider higher doses, longer treatment periods and/or alternative cannabinoid combinations.

Clincaltrals.gov identifier: NCT01502046

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Acknowledgments

We thank the patients and their families who participated in the trial for their endeavor. We also thank GW Pharmaceuticals for their kind support.

Author information

Authors and Affiliations

  1. Neurology Department, Hospital Ramón y Cajal, Carretera de Colmenar Km 9.100, 28034, Madrid, Spain

    Jose Luis López-Sendón Moreno, Juan García Caldentey, Patricia Trigo Cubillo, Guillermo García Ribas, M. A. Alonso Alonso Arias & Justo García de Yébenes Prous

  2. Neurobiology Department, Hospital Ramón y Cajal, Madrid, Spain

    Carolina Ruiz Romero

  3. Instituto de Salud Músculoesquelética, Madrid, Spain

    María Jesús García de Yébenes

  4. Fundación Hospital de Alcorcón, Madrid, Spain

    Rosa María Tolón

  5. Department of Biochemistry and Molecular Biology I, Faculty of Biology, Complutense University, Madrid, Spain

    Ismael Galve-Roperh, Eva Resel & Manuel Guzmán

  6. Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain

    Jose Luis López-Sendón Moreno, Ismael Galve-Roperh, Onintza Sagredo, Sara Valdeolivas, Eva Resel, Javier Fernández Ruiz, Manuel Guzmán & Justo García de Yébenes Prous

  7. Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain

    Jose Luis López-Sendón Moreno, Ismael Galve-Roperh, Onintza Sagredo, Sara Valdeolivas, Eva Resel, María Laura García-Bermejo, Javier Fernández Ruiz & Manuel Guzmán

  8. Department of Biochemistry and Molecular Biology III, Faculty of Medicine, Complutense University, Madrid, Spain

    Onintza Sagredo, Sara Valdeolivas & Javier Fernández Ruiz

  9. Department of Organic Chemistry I, Faculty of Chemistry, Complutense University, Madrid, Spain

    Silvia Ortega-Gutierrez

Authors
  1. Jose Luis López-Sendón Moreno
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  2. Juan García Caldentey
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  3. Patricia Trigo Cubillo
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  4. Carolina Ruiz Romero
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  5. Guillermo García Ribas
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  6. M. A. Alonso Alonso Arias
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  8. Rosa María Tolón
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  9. Ismael Galve-Roperh
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  10. Onintza Sagredo
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  15. Javier Fernández Ruiz
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Corresponding author

Correspondence to Jose Luis López-Sendón Moreno.

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Funding sources for the study

This study was sponsored by Fundación para la Investigación Biomédica del Hospital Universitario Ramón y Cajal, GW Pharmaceuticals Ltd and Comunidad de Madrid (Grant S2010/BMD-2308).

Financial disclosure

García Caldentey, J, Trigo Cubillo, P; Ruiz Romero, C; García Ribas, G; Alonso Arias, MA; García de Yébenes M.J; Tolón Rafael, RM; Galve-Roperh, I; Resel, E; Ortega-Gutierrez, S; García-Bermejo, ML; Guzmán, M; García de Yébenes Prous, J report no disclosures.

Conflicts of interest

López-Sendón Moreno J.L.: has received travel grants from Lundbeck and Krka pharmaceuticals. No conflicts of interest to disclose. Sagredo O, Valdeolibas S and Fernández-Ruiz J are recipient of a grant from GW Pharmaceuticals.

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Supplemental Data (Fig. 1, Supplementary Material: Consort Flow Diagram; Table 1, Supplementary Material: Basal Clinic Characteristics) (DOC 67 kb)

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López-Sendón Moreno, J., García Caldentey, J., Trigo Cubillo, P. et al. A double-blind, randomized, cross-over, placebo-controlled, pilot trial with Sativex in Huntington’s disease. J Neurol 263, 1390–1400 (2016). https://doi.org/10.1007/s00415-016-8145-9

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  • DOI: https://doi.org/10.1007/s00415-016-8145-9

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