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Disulfiram as a Modulator of Amyloid Precursor Protein-processing

NCT03212599 — Completed, 17 participants, Johannes Gutenberg University Mainz

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Quantitative Analysis of the Expression of Dementia-relevant Genes by Intake of the Drug Disulfiram

RegistryNCT03212599, acronym DIMAP
StatusCompleted
Study typeObservational
Enrollment17 (Actual)
SponsorJohannes Gutenberg University Mainz (Other)
ConditionsAlcohol Addiction
InterventionsDisulfiram (Drug)
Datesstart 2013-05-01, primary completion 2016-06-01, completion 2017-07-01, first posted 2017-07-11, last updated 2017-07-24

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-Summary

A causal therapeutic approach for treatment of Alzheimer's disease has not been established so far. The protein ADAM10 represents a promising target for an A-beta peptide preventing strategy. Treatment of human neuronal cells with Disulfiram, a drug which is used in clinical routine for recrudescence prevention of alcohol dependency, revealed an increased expression of ADAM10. This finding indicates a neuroprotective potential of Disulfiram. The investigators' research purpose aims at the verification of the results obtained in cell culture experiments in the human organism. Therefore, include alcohol addicted patients were included, which take the drug Disulfiram for recrudescence prevention, in our study. Patients are recruited from the patient-collective of the University Medical Center Mainz and the Central Institute for Mental Health Mannheim. Blood samples (max. 5 ml) are taken from the participants before the intake of Disulfiram and about two weeks after treatment. Demographic data are collected (such as age or onset of addiction). Gene expression is analyzed via reverse transcription polymerase chain reaction(RT-PCR) from blood cell-derived messenger ribonucleic acid (mRNA).

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+Arms and interventions

  • Disulfiram (Drug), also known as Antabus: alcohol addicted patients receive an oral Disulfiram application as recrudescence prevention after successful detoxication

+Outcome measures

Primary outcomes

  • expression of ADAM10 [August 2016]: expression of ADAM10 in the collected blood samples measured by quantitation of the mRNA amount using RealTime-RT-PCR.

+Eligibility

Sex: All, ages: 20 Years to 60 Years, accepts healthy volunteers

Inclusion Criteria:

ambulant or stationary patients, which receive Disulfiram for recrudescence prevention

Exclusion Criteria:

Diagnosed Alzheimer's dementia Previous Disulfiram treatment less than four weeks before baseline blood collection

+Publications

  • Results publication: Saifi MA, Shaikh AS, Kaki VR, Godugu C. Disulfiram prevents collagen crosslinking and inhibits renal fibrosis by inhibiting lysyl oxidase enzymes. J Cell Physiol. 2022 May;237(5):2516-2527. doi: 10.1002/jcp.30717. Epub 2022 Mar 13. PMID 35285015

+Investigators

  • Kristina Endres, Principal investigator, Medical Center Johannes Gutenberg University

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