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Evaluation of the Feasibility, Safety and Efficacy of the Use of Intravenous Infusions of Adenosine Triphosphate (ATP) in People Affected by Moderate to Severe Alzheimer’s Disease: A Double-Blind Masked Clinical Trial for Dose Finding

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The Journal of Prevention of Alzheimer's Disease Aims and scope Submit manuscript

Abstract

Background

There are currently no drug therapies modifying the natural history of patients suffering Alzheimer’s disease (AD). Most recent clinical trials in the field include only subjects in early stage of the disease, while patients with advanced AD are usually not represented.

Objectives

To evaluate the feasibility, safety and efficacy of systemic infusions of adenosine triphosphate (ATP) in patients with moderate to severe AD, and to select the minimum effective dose of infusion.

Design

A phase IIb, randomized, double-blind, placebo-controlled clinical trial investigates.

Participants

A total of 20 subjects with moderate or severe AD were included, 16 in the treatment group and 4 in the placebo group (4:1 randomization) at two dosage regimens, 6-hour or 24-hour infusions.

Results

The proof-of-concept study was successfully conducted, with no significant deviations from the study protocol and no serious adverse events reported. Regarding efficacy, only marginal differences were observed between ATP and placebo arms for H-MRS and MMSE variables.

Conclusions

Our study demonstrates that the use of ATP infusion as therapy is feasible and safe. Larger studies are however needed to assess the efficacy of ATP in moderate to severe AD.

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Availability of data and materials

The datasets used and/or analysed during the current study, as well as the two independent statistical analysis reports from the Medical Statistics Core Facility of IDIBAPS - Hospital Clínic Barcelona and the Andalusian Bioinformatics Research Centre (CAEBi), are available from the corresponding author on reasonable request.

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Acknowledgements

We would like to thank patients and controls who participated in this project. We are indebted to the Trinitat Port-Carbó legacy and her family for their support of Fundació ACE research programs. A. R. has received support from CIBERNED (Instituto de Salud Carlos III (ISCIII), the EU/EFPIA Innovative Medicines Initiative Joint Undertaking, ADAPTED Grant No. 115975, from EXIT project, EU Euronanomed3 Program JCT2017 Grant No. AC17/00100, from PREADAPT project. Joint Program for Neurodegenerative Diseases (JPND) Grant No. AC19/00097, and from grants PI13/02434, PI16/01861 BA19/00020, and PI19/01301. Acción Estratégica en Salud, integrated in the Spanish National RCDCI Plan and financed by Instituto de Salud Carlos III (ISCIII)- Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER - “Una manera de Hacer Europa”), by Fundación bancaria “La Caixa” and Grífols SA (GR@ACE project).

Funding

This work has been supported by the Dirección General the Farmacia. Instituto de Salud Carlos III (ISCIII). Ministerio de Innovacion Ciencia y Universidades. Gobierno España. Grant number EC11-358 and Fundació ACE.

Author information

Authors and Affiliations

  1. Research Center and Memory Clinic, Fundació ACE, Barcelona Alzheimer Treatment and Research Centre, Institut Català de Neurociències Aplicades, Universitat Internacional de Catalunya (UIC), Barcelona, Spain

    Agustín Ruiz, D. Sánchez, A. Lafuente, G. Ortega, M. Buendía, J. Papasey, M. E. Palacio, C. Abdelnour, L. Tárraga & M. Boada

  2. Networking Research Center on Neurodegenerative Diseases (CIBERNED), Madrid, Spain

    Agustín Ruiz, G. Ortega, C. Abdelnour, L. Tárraga & M. Boada

  3. Neurophysiology Unit, Hospital Quirón Dexeus, Barcelona, Spain

    S. Y. Jimeno

  4. Diagnosis Imaging Unit, Hospital Quirón Dexeus, Barcelona, Spain

    F. P. Badia

  5. Clinical Pharmacy, Hospital Universitari de la Vall d’Hebron, Barcelona, Spain

    M. E. Palacio

  6. Department of Experimental Psychology, School of Psychology, Complutense University of Madrid, Madrid, Spain

    F. Ramírez-Toraño & F. Maestú

  7. Laboratory of Cognitive and Computational Neuroscience, Center for Biomedical Technology, Technical University of Madrid and Complutense University of Madrid, Madrid, Spain

    F. Ramírez-Toraño & F. Maestú

  8. Andalusian Bioinformatics Research Centre (CAEBi), Seville, Spain

    M. E. Sáez

  9. Department of Internal Medicine, Maastricht University, Maastricht, the Netherlands

    P. C. Dagnelie

  10. School for Cardiovascular Diseases (CARIM), Maastricht University, Maastricht, the Netherlands

    P. C. Dagnelie

Authors
  1. Agustín Ruiz
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  2. D. Sánchez
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  3. A. Lafuente
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  4. G. Ortega
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  11. F. Ramírez-Toraño
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  15. P. C. Dagnelie
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  16. M. Boada
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Contributions

AR conceived this treatment. AR, LT, MBo, MEP, PCD designed the research program and the clinical trial. DS, AL, GO, MBu, JP, MEP, CA, SYJ, FPB, implemented the clinical trial, study. AR, MES, FRT, FM, PCD and MBo interpreted the CT results. MES and AR wrote the manuscript and all authors revised the text and contributed to the ms editing.

Corresponding author

Correspondence to Agustín Ruiz.

Ethics declarations

This clinical trial was conducted in compliance with the declaration of Helsinki. All participants (or their legal representative) provided written informed consent prior to screening. The final study protocol and informed consent documentation were reviewed and approved by the Ethics Committee from Hospital Clinic (Barcelona). The Study was registered at the EU Clinical Trials Register (EudraCT: 2013-004593-95) and approved by the Spanish Agency for Medicines and Medical Devices (AEMPS).

Additional information

How to cite this article: A. Ruiz, D. Sánchez, A. Lafuente, et al. Evaluation of the Feasibility, Safety and Efficacy of the Use of Intravenous Infusions of Adenosine Triphosphate (ATP) in People Affected by Moderate to Severe Alzheimer’s Disease: A Double-Blind Masked Clinical Trial for Dose Finding. J Prev Alz Dis 2022;3(9):425-434; https://doi.org/10.14283/jpad.2022.38

Competing interests

The authors declare that they have no competing interests related to this manuscript. AR is member of the Scientific Advisory Board of Landsteiner Genmed and AMBAR program (Grifols). MES is member of the Scientific Advisory Board of Landsteiner Genmed.

Trial registration

EudraCT: 2013-004593-95. Registered 13th February 2014, https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-004593-95/ES.

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Ruiz, A., Sánchez, D., Lafuente, A. et al. Evaluation of the Feasibility, Safety and Efficacy of the Use of Intravenous Infusions of Adenosine Triphosphate (ATP) in People Affected by Moderate to Severe Alzheimer’s Disease: A Double-Blind Masked Clinical Trial for Dose Finding. J Prev Alzheimers Dis 9, 425–434 (2022). https://doi.org/10.14283/jpad.2022.38

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