The NeXT Study; The Netherlands XTC Toxicity Study

• ClinicalTrials.gov Identifier: NCT00235768
• Recruitment Status: Completed
• First Posted: October 10, 2005
• Last Update Posted: October 10, 2005
• Sponsor: UMC Utrecht
• Collaborators: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA); University of Amsterdam, Bonger Institute of Criminology; Erasmus Medical Center
• Information provided by: UMC Utrecht

Tracking Information

• First Submitted Date: October 6, 2005
• First Posted Date: October 10, 2005
• Last Update Posted Date: October 10, 2005
• Study Start Date: April 2002
• Primary Completion Date: Not Provided
• Current Primary Outcome Measures: Not Provided
• Original Primary Outcome Measures: Not Provided
• Change History: No Changes Posted
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: The NeXT Study; The Netherlands XTC Toxicity Study
• Official Title: Neurotoxicity of Ecstasy: Causality, Course and Clinical Relevance
• Brief Summary: The purpose of this study is to investigate the possible neurotoxic effects of the party-drug Ecstasy (MDMA)on brain and brain function in humans. Main research questions concern the causality, course and clinical relevance of the neurotoxicity of ecstasy
• Detailed Description: The study aims to investigate the causality, course and clinical relevance of the observed neurotoxicity in het human brain among users of the popular recreational drug 3,4-methylenedioxymethamphetamine (MDMA). Studies in animals and non-human primates suggest that MDMA is toxic toward brain serotonin neurons at doses that overlap those used by humans. Much less is known about the effects of this drug on the human brain. Recent studies, however, suggest that MDMA might also be neurotoxic to 5-HT neurons in humans, and that it is associated with functional consequences, such as memory impairment and depression. However, these studies have been retrospective and potentially vulnerable to selection bias and confounding. Clearly, only a prospective study can ascertain that recreational XTC is neurotoxic in humans. However, given the existing data such a study is ethically not acceptable. In the present project, therefore, we have chosen a naturalistic study using a combination of prospective and retrospective approaches: a prospective study among 200 XTC naive subjects with a high-risk profile for first XTC use with a two-year follow up of 50 incident-, and 50 continuously XTC naive subjects, and a retrospective design of 25 subjects with and 25 subjects without prior exposure to XTC selected from a large representative cohort (N=1600) that was prospectively followed from the age of 12. In addition, a cross sectional design is used of 70 subjects with variation in type and amount of drugs used, besides a history of frequent XTC use. Among the 50 incident cases and the sample of 50 continuously XTC-naive subjects in the prospective cohort, indicators of neurotoxicity (SPECT,1H-MRS), markers of neuronal injury (fMRI, Perfusion MRI), and clinical assessments of memory, mood and personality prior to any XTC use will be compared with the same parameters two years later, i.e. after XTC user has taken place in the incident cases. In the retrospective cohort, subjects with lifetime XTC exposure will be compared with XTC naive subjects on the same neurotoxicity, neural injury and psychopathology parameters, controlling for potential confounders that were assessed prior to the first use of XTC. In the cross sectional cohort, all subjects will be assessed on the same neurotoxicity, neural injury and psychopathology parameters, controlling for the confounding effects of the use of other psychoactive drugs besides XTC. The combined results will result in conclusions that can be validly used in prevention messages, clinical decision making and the development op a national XTC policy.
• Study Type: Observational
• Study Design: Observational Model: Defined Population; Time Perspective: Other
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• Sampling Method: Not Provided
• Study Population: Not Provided

Condition

• Ecstasy (Drug)
• N-Methyl-3,4-Methylenedioxymethamphetamine
• Psychopathology

• Intervention: Not Provided
• Study Groups/Cohorts: Not Provided

Publications *

• de Win MM, de Jeu RA, de Bruin K, Habraken JB, Reneman L, Booij J, den Heeten GJ. Validity of in vivo [123I]beta-CIT SPECT in detecting MDMA-induced neurotoxicity in rats. Eur Neuropsychopharmacol. 2004 May;14(3):185-9.
• de Win MM, Reneman L, Reitsma JB, den Heeten GJ, Booij J, van den Brink W. Mood disorders and serotonin transporter density in ecstasy users--the influence of long-term abstention, dose, and gender. Psychopharmacology (Berl). 2004 May;173(3-4):376-82. Epub 2004 Jan 15.
• Reneman L, Booij J, Majoie CB, Van Den Brink W, Den Heeten GJ. Investigating the potential neurotoxicity of Ecstasy (MDMA): an imaging approach. Hum Psychopharmacol. 2001 Dec;16(8):579-588.
• Reneman L, Endert E, de Bruin K, Lavalaye J, Feenstra MG, de Wolff FA, Booij J. The acute and chronic effects of MDMA ("ecstasy") on cortical 5-HT2A receptors in rat and human brain. Neuropsychopharmacology. 2002 Mar;26(3):387-96.
• Reneman L, Booij J, de Bruin K, Reitsma JB, de Wolff FA, Gunning WB, den Heeten GJ, van den Brink W. Effects of dose, sex, and long-term abstention from use on toxic effects of MDMA (ecstasy) on brain serotonin neurons. Lancet. 2001 Dec 1;358(9296):1864-9.
• Reneman L, Majoie CB, Habraken JB, den Heeten GJ. Effects of ecstasy (MDMA) on the brain in abstinent users: initial observations with diffusion and perfusion MR imaging. Radiology. 2001 Sep;220(3):611-7.
• De Win MM, Jager G, Vervaeke HK, Schilt T, Reneman L, Booij J, Verhulst FC, Den Heeten GJ, Ramsey NF, Korf DJ, Van den Brink W. The Netherlands XTC Toxicity (NeXT) study: objectives and methods of a study investigating causality, course, and clinical relevance. Int J Methods Psychiatr Res. 2005;14(4):167-85.

Recruitment Information

• Recruitment Status: Completed
• Enrollment (submitted: October 6, 2005): 225
• Original Enrollment: Same as current
• Study Completion Date: July 2005
• Primary Completion Date: Not Provided

Eligibility Criteria

Inclusion Criteria:

• between 18 - 35 years of age

Exclusion Criteria:

• severe medical or neuropsychiatric illness
• use of prescribed psychotropic medications such as SSRI's
• use of intravenous drugs
• pregnancy
• contra-indications for MRI investigation

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 35 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Netherlands

Administrative Information

• NCT Number: NCT00235768
• Other Study ID Numbers: ZonMW 310-00-036
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Not Provided
• Original Responsible Party: Same as current
• Current Study Sponsor: UMC Utrecht
• Original Study Sponsor: Same as current

Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• University of Amsterdam, Bonger Institute of Criminology
• Erasmus Medical Center

Investigators

• Study Director: Wim van den Brink, MD PhD; University of Amsterdam, Academic Medical Center Amsterdam, Dep of Psychiatry
• Study Director: Nick F Ramsey, PhD; University Medical Center Utrecht, Dep of Psychiatry
• Study Director: Dirk J Korf, PhD; University of Amsterdam, Bonger Institute for Criminology
• Principal Investigator: Maartje ML de Win, MD; University of Amsterdam, Academic Medical Center Amsterdam, Dep of Radiology
• Principal Investigator: Gerry Jager, MSc; University Medical Center Utrecht, Dep of Psychiatry
• Principal Investigator: Hylke KE Vervaeke, MSc; University of Amsterdam, Bonger Institute of Criminology

• PRS Account: UMC Utrecht
• Verification Date: October 2004