NeutropeniaAAPsNCT06107322
Hematological Effects of Atypical Antipsychotics (AAPs) in a Geriatric Population: What is the Role of 5-HT2 Receptors
An observational study of Neutropenia, run by University Hospital, Strasbourg, France at 1 site in France.
Trial summary
White lineage abnormalities and in particular neutropenia and agranulocytosis are known and increasingly studied adverse effects of antipsychotics, particularly second generation. Read more about this study
- Who is it for?
- Ages 65 years and older
- Conditions the study is for
- Neutropenia
- How many people
- 20 participants
- Where
- 1 siteFrance
- Study dates
- 1 Mar 2023to 23 Mar 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 65 years and older
- All sexes
- Older adult
Study population: Major subject (≥ 65 years old) having indication for the introduction of the neuroleptic indicated
Who may be able to join
- Major subject (≥ 65 years old)
- Subject hospitalized in Geriatric Internal Medicine, in Geriatric Follow-up Care and Rehabilitation, in a Long-Term Care Unit or Important Medical-Technical Care, in a Reinforced Accommodation Unit or in a Cognitive-Behavioral Unit at Strasbourg University Hospitals)
- Subject not opposing the reuse of their data for the purposes of this research.
- Indication for the introduction of the neuroleptic indicated
- Available dosage and frequency of administration and duration of treatment
Who cannot join
- Subject having expressed opposition to participating in the study
- Presence of a neuroleptic before admission to the University Hospitals of Strasbourg, excluding readmission of a patient included
- Neuroleptics not present on the discharge prescription for long-term treatment
- Neuroleptics prescribed for less than 48 hours
- Presence of a white lineage anomaly prior to the initiation of neuroleptic treatment
- Patient contraindicated for taking a long-term neuroleptic.
- Hematological disease with white lineage abnormality (lymphoma, leukemia, myelodysplasia, mye syndrome
Trial locations and contacts
1 site in 1 country.
France1 site, 1 recruiting
- Recruiting
Service de Pharmacie - Stérilisation - CHU de Strasbourg - France
Strasbourg, 67091
Estelle AYME-DIETRICH, Pharm, PhD, 33 3 68 85 30 83, estelle.ayme@chru-strasbourg.fr
Arthur ESQUER, PhD, 33 3 68 85 30 83, arthur.esquer@chru-strasbourg.fr
About this study
Official title: Retrospective Study on the Hematological Effects of Atypical Antipsychotics (AAPs) in a Geriatric Population: What is the Role of 5-HT2 Receptors
White lineage abnormalities and in particular neutropenia and agranulocytosis are known and increasingly studied adverse effects of antipsychotics, particularly second generation. White lineage abnormalities have been found with each of the drugs in this class even if progression to agranulocytosis is rarer with drugs other than Clozapine.
The infections, sometimes serious, induced by these adverse effects have largely led to limiting the use of second generation antipsychotics, and in particular clozapine, to the treatment of patients resistant to other first or second line treatments.
Read more
Several hypotheses have been put forward: the first is that of an immuno-allergic reaction mediated by eosinophils with increased sensitivity depending on the HLA type, another that of a direct toxic effect of clozapine or its main metabolite, N -demethylclozapine and a third attributes hematological disorders to catecholaminergic inhibition which prevents the differentiation of CD34+ hematopoietic stem cells into leukocytes, after blocking dopaminergic and/or beta-adrenergic receptors.
More recently, a new hypothesis is emerging following scandals particularly in France linked to Benfluorex (Mediator®), Dexfenfluramine (Isomeride®) and Fenfluramine (Pondéral®). Indeed, by studying the cellular mechanisms linked to the stimulation of the 5-HT2B receptor by their common metabolite Nordexfenfluramine, researchers from the NeuroCardiovascular pharmacology and toxicology laboratory in Strasbourg have demonstrated that the stimulation of 5-HT2BR mobilizes CD34+ cells in blood from the bone marrow and selective blocking of 5-HT2B receptors, reduces the number of leukocytes in the blood, mainly neutrophils and lymphocytes, further decreasing their blood concentration with exposure time.
Read the detailed description
The investigators chose as their study population an elderly to very elderly population, hospitalized or residing in the Geriatrics center of a university hospital. Indeed, apart from resistant schizophrenia, clozapine is the reference antipsychotic in behavioral disorders associated with the dementia of Parkinson's disease, Lewy body disease and other atypical parkinsonian syndromes, particularly because of its antagonism. dopaminergic less important. The absence of equivalent therapy justifies studying the occurrence of adverse effects precisely in this population. Studies have already taken place on clozapine in this indication but to our knowledge none have sought to demonstrate the occurrence of white lineage disorders based on its effects on 5-HT2 receptors.
This study could provide a better understanding of the role and function of serotonin receptors of the 5-HT2 subtype, on the differentiation/mobilization of hematopoietic cells, with the clinical challenge of better prescription in the geriatric population, often fragile, of atypical neuroleptics which are the only therapeutic alternative in the delusional disorders of patients with Lewy bodies but also used in other neurodegenerative disorders.
- Conditions
- Neutropenia
- Keywords
- Neutropenia, Atypical antipsychotics (AAPs), 5-HT2 receptors, Hematological effects
- Medical subject headings
- Neutropenia
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of neutrophils per liter of blood
Measured: 1 hour after blood collection
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Oct 2023
- Study start1 Mar 2023
- Primary completionMar 2024 (estimated)
- Study completion23 Mar 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NeutropeniaStudies of the same condition, open and under way.
- More trials run by University Hospital, Strasbourg, FranceThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Retrospective
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Strasbourg, France
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06107322
- Sponsor's protocol ID
- 8902
- Acronym
- AAPs
- Status last verified
- Oct 2023
- First submitted
- 24 Oct 2023
- Last updated
- 30 Oct 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Retrospective Study on the Hematological Effects of Atypical Antipsychotics (AAPs) in a Geriatric Population: What is the Role of 5-HT2 Receptors
- ClinicalTrials.gov ID
- NCT06107322
- Acronym / sponsor ID
- AAPs / 8902
- Conditions
- Neutropenia
- Keywords
- Neutropenia, Atypical antipsychotics (AAPs), 5-HT2 receptors, Hematological effects
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- University Hospital, Strasbourg, FranceUniversity, hospital or other
- Study start
- 1 Mar 2023 (actual)
- Primary completion
- Mar 2024 (estimated)
- Study completion
- 23 Mar 2024 (estimated)
- First posted
- 30 Oct 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
White lineage abnormalities and in particular neutropenia and agranulocytosis are known and increasingly studied adverse effects of antipsychotics, particularly second generation. White lineage abnormalities have been found with each of the drugs in this class even if progression to agranulocytosis is rarer with drugs other than Clozapine.
The infections, sometimes serious, induced by these adverse effects have largely led to limiting the use of second generation antipsychotics, and in particular clozapine, to the treatment of patients resistant to other first or second line treatments.
Several hypotheses have been put forward: the first is that of an immuno-allergic reaction mediated by eosinophils with increased sensitivity depending on the HLA type, another that of a direct toxic effect of clozapine or its main metabolite, N -demethylclozapine and a third attributes hematological disorders to catecholaminergic inhibition which prevents the differentiation of CD34+ hematopoietic stem cells into leukocytes, after blocking dopaminergic and/or beta-adrenergic receptors.
More recently, a new hypothesis is emerging following scandals particularly in France linked to Benfluorex (Mediator®), Dexfenfluramine (Isomeride®) and Fenfluramine (Pondéral®). Indeed, by studying the cellular mechanisms linked to the stimulation of the 5-HT2B receptor by their common metabolite Nordexfenfluramine, researchers from the NeuroCardiovascular pharmacology and toxicology laboratory in Strasbourg have demonstrated that the stimulation of 5-HT2BR mobilizes CD34+ cells in blood from the bone marrow and selective blocking of 5-HT2B receptors, reduces the number of leukocytes in the blood, mainly neutrophils and lymphocytes, further decreasing their blood concentration with exposure time.
Detailed description
The investigators chose as their study population an elderly to very elderly population, hospitalized or residing in the Geriatrics center of a university hospital. Indeed, apart from resistant schizophrenia, clozapine is the reference antipsychotic in behavioral disorders associated with the dementia of Parkinson's disease, Lewy body disease and other atypical parkinsonian syndromes, particularly because of its antagonism. dopaminergic less important. The absence of equivalent therapy justifies studying the occurrence of adverse effects precisely in this population. Studies have already taken place on clozapine in this indication but to our knowledge none have sought to demonstrate the occurrence of white lineage disorders based on its effects on 5-HT2 receptors.
This study could provide a better understanding of the role and function of serotonin receptors of the 5-HT2 subtype, on the differentiation/mobilization of hematopoietic cells, with the clinical challenge of better prescription in the geriatric population, often fragile, of atypical neuroleptics which are the only therapeutic alternative in the delusional disorders of patients with Lewy bodies but also used in other neurodegenerative disorders.
Study design
- Observational model
- Case-control
- Time perspective
- Retrospective
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Age groups
- Older adult
- Study population
- Major subject (≥ 65 years old) having indication for the introduction of the neuroleptic indicated
Key inclusion criteria (5 listed)
- Major subject (≥ 65 years old)
- Subject hospitalized in Geriatric Internal Medicine, in Geriatric Follow-up Care and Rehabilitation, in a Long-Term Care Unit or Important Medical-Technical Care, in a Reinforced Accommodation Unit or in a Cognitive-Behavioral Unit at Strasbourg University Hospitals)
- Subject not opposing the reuse of their data for the purposes of this research.
- Indication for the introduction of the neuroleptic indicated
- Available dosage and frequency of administration and duration of treatment
Key exclusion criteria (7 listed)
- Subject having expressed opposition to participating in the study
- Presence of a neuroleptic before admission to the University Hospitals of Strasbourg, excluding readmission of a patient included
- Neuroleptics not present on the discharge prescription for long-term treatment
- Neuroleptics prescribed for less than 48 hours
- Presence of a white lineage anomaly prior to the initiation of neuroleptic treatment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Number of neutrophils per liter of blood
Time frame: 1 hour after blood collection
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Oct 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Neutropenia, run by University Hospital, Strasbourg, France at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 30 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Estelle AYME-DIETRICH, Pharm, PhD (33 3 68 85 30 83, estelle.ayme@chru-strasbourg.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of neutrophils per liter of blood (time frame: 1 hour after blood collection). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Oct 2023.