Alzheimer DiseasePhase 2drainADNCT03417986
Clinical Trial to Explore the the Amyloid Beta Draining Effect of Thiethylperazine (TEP) in Subjects With Newly Diagnosed Early-to-mild Dementia Due to Alzheimer's Disease (AD) in Comparison to Healthy Volunteers
A Phase 2 study testing TEP in people with Alzheimer Disease, run by Immungenetics AG at 2 sites in Germany.
Trial summary
This proof-of-mechanism clinical trial study will test the efficacy and safety of thiethylperazine (TEP) in subjects with early onset of Alzheimer's Disease (AD). There is a strong scientific rationale for this study: TEP is a very well-known substance that has been available since 1961 and approved for the prevention… Read more about this study
- Who is it for?
- Ages 55 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Alzheimer Disease
- What is being tested?
- TEP
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 2 sitesGermany
- Study dates
- 24 Nov 2017to 22 Oct 2021
- Phase
- Phase 2
- 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 55 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- For AD subject
- Newly diagnosed (< 12 months) early-to-mild Alzheimer's disease as classified by a Mini-Mental State Examination (MMSE) Score of 25-18 reconfirmed at screening
- AD diagnosis confirmed by recommended examinations in accordance with German DGN (Deutsche Gesellschaft für Neurologie)/DGPPN (Deutsche Gesellschaft für Psychiatrie und Psychotherapie,Psychosomatik und Nervenheilkunde) S3 Guideline "Dementia" and to standard at the clinical unit by:
- psychometric and cognitive tests
- lumbar puncture in subjects with uncertain AD diagnosis following central nervous system (CNS) imaging
- Clinical Dementia Rating (global CDR) is 0.5 or 1. Memory box score must be at least 0.5. Isolated or predominant episodic memory deficit, manifested as memory performance in the Logical Memory subscale (Delayed Paragraph Recall) from the Wechsler Memory Scale-III 1 below age adjusted norms, according to hospital standard)
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- AD subject has full legal competence according to investigator opinion
- Ability to comply with requirements or cognitive and other testing for the entire length of the trial available
- For healthy volunteer
- Subject is a non-demented volunteer, based on the assessment of medical history, physical examination and clinically laboratory data at screening as determined by the Investigator
- For AD subject and healthy volunteer
- Age > 55 - < 75 years
- Written informed consent to participate within this trial
- Subject is on stable dose for at least 3 month prior to screening when receiving protocol-allowed concomitant medications at screening (e.g. acetylcholinesterase inhibitors, NMDA (N-methyl-D-aspartate) receptor antagonists)
- For subject receiving anticholinergic agents, oral corticosteroids, propranolol, clonidine, antihistamines other than cetirizin and EBSTEL® a washout period of 4 weeks prior to screening must be completed. Concerning anticholinergic agents in Group 1a: only for high- to medium-potency anticholinergic agents a washout period of 4 weeks prior to screening must be completed.
- Post-menopausal females (post menopausal amenorrhea for at least 2 years or surgically sterilized (hysterectomy), tubal ligation is not acceptable)
- Male subjects with reproductive potential, and have not been surgically sterilized, that have been informed and agreed to that he and his partner must use a highly effective method of contraception (Pearl Index <1%) such as implants, injectables, combined oral contraceptives, or hormonal intrauterine devices (IUDs), or refrain from sexual intercourse during the trial and until 3 months after completion of the trial
- Good general health with no additional disease states that could interfere with the trial due to the investigator's assessment
Who cannot join
- CSF cut-off values identified during routine Neurochemical Dementia Diagnostics
- History or evidence of other significant neurological disease of the Central Nervous System (such as Parkinson's disease, multi-infarct dementia, fronto-temporal dementia, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supra nuclear palsy, epilepsy, myasthenia gravis, subdural hematoma or multiple sclerosis)
- History of significant head trauma followed by persistent neurologic defaults or known structural brain abnormalities
- Significant neuroimaging abnormalities, previously known or discovered on the MRI scan, including evidence of infection, infarction (> 3 mm in size), brain tumors (other than small meningiomas), or other focal lesions, multiple lacunas or lacunas in a critical memory structure or severe confluent microvascular disease (but not mild white matter changes, which are frequent with aging)
- History or evidence of moderate congestive heart failure defined by the New York Heart Association criteria (class I-IV)
- Clinical relevant ECG findings, abnormalities, e.g. pro-arrhythmic potential/effects on QT interval (QTc >450 msec for males, >470 msec for females, confirmed by manual assessment of ECG parameters)
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- History of new cardiovascular event within the last 6 months
- Resting sitting vital signs: Systolic blood pressure ≤ 100 mmHg or ≥ 165 mmHg, Diastolic blood pressure ≤ 60 mmHg or ≥ 100 mmHg, heart rate ≤ 50 beats/min or ≥ 90 beats/min9. Clinically significant renal disease or insufficiency, including but not limited to creatinine value of >1.5 mg/dl
- Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), total bilirubin, or alkaline phosphatase >2.5 times the upper limit of normal laboratory range, or history of severe hepatobiliary disease (e.g. hepatitis B or C, or cirrhosis) without enzyme elevation
- Positive tested for hepatitis B surface antigen (HBsAG) or hepatitis C virus/antibodies (anti-HCV) for the first time within the last 6 months prior to the Screening Visit
- Positive tested for human immunodeficiency virus (HIV) at Screening Visit
- Fasting triglycerides >2.5 times of the upper limit of normal
- Uncontrolled diabetes (FBG > 150 mg/dl)
- Coagulopathy or any kind of anti-coagulant therapy
- Extrapyramidal syndrome
- Elevation of prolactin, e.g. subject with prolactin-dependent breast cancer or pituitary tumor
- History of severe psychiatric disease like psychotic disorder or current anxiolytic or neuroleptic therapy (for dementia-related or other psychiatric disorder) within the last 3 months of enrolment
- Chronic depression or bipolar disorder or history of major depression within the past 2 years or history of any episode of treatment-resistant depression (requiring > 1 antidepressants, Electroconvulsive Therapy (ECT) etc.)
- Significant history of alcohol abuse or drug abuse within the past 6 months (at the judgment of the investigator)
- Current treatment with TEP or treatment up to 24 month prior to screening
- Known incompatibility of TEP or phenothiazines
- Subject is receiving the following treatment that may interact with TEP, e.g. adrenaline, tricyclic antidepressants, narcotics, bromocriptine, MAO (monoamine oxidase) inhibitors, CYP2D6 inhibitors, tramadol, pentetrazol, levodopa, anticonvulsants, medication causing extrapyramidal symptoms increases the likelihood of central nervous system side effects
- Participation in a clinical trial involving another investigational drug within 4 weeks prior to screening visit
- Women of child bearing potential or women who are pregnant or nursing
- Male subjects with reproductive potential who refuse to use adequate means of contraception during and up to 3 months after stopping treatment with TEP
Trial locations and contacts
2 sites in 1 country.
Germany2 sites
Klinik für Psychiatrie und Psychotherapie Universitätsmedizin Göttingen
Göttingen, 37075
Zentralinstitut für seelische Gesundheit, Medizinische Fakultät Mannheim, Universität Heidelberg,
Mannheim, 68159
About this study
Official title: An Open-label, Multicenter, Controlled Pharmaco-dynamic Clinical Trial to Explore the the Amyloid Beta Draining Effect of Thiethylperazine (TEP) in Subjects With Newly Diagnosed Early-to-mild Dementia Due to Alzheimer's Disease in Comparison to Healthy Volunteers
This proof-of-mechanism clinical trial study will test the efficacy and safety of thiethylperazine (TEP) in subjects with early onset of Alzheimer's Disease (AD). There is a strong scientific rationale for this study: TEP is a very well-known substance that has been available since 1961 and approved for the prevention and treatment of nausea, vomiting as well as vertigo. Therefore, it has a well understood pharmacologic background and promising safety data. Using AD mouse models, it has been recently discovered and confirmed that TEP promotes transport of toxic Aβ from the brain into the blood. More importantly, it has also been demonstrated to improve learning deficits in mice. The striking biological effect of TEP in preclinical testing and its known safety and toxicity profile encourages the investigators to investigate this in a multicenter clinical trial in subjects with early-to-mild AD in comparison to healthy volunteers. The investigators will assess whether TEP is able to enhance the transport of Aβ peptides from the brain into the blood in subjects with early-to-mild AD and improves cognitive efficacy.
- Conditions
- Alzheimer Disease
- Being tested
- TEP
- Keywords
- Thiethylperazine, Alzheimer Disease
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TEPDrug
Also called Thiethylperazine
For safety reasons the clinical trial will first enroll 14 subjects (7 patients and 7 healthy volunteers) for Group 1a receiving 26 mg TEP daily for 4 days with subsequent safety evaluation, based on adverse events and the safety parameters discussed in the protocol. A second set of patients (Group 1b), which will receive a higher dosage of 52 mg per day for 4 days will be enrolled optionally after recommendation to continue and subsequently treatment Group 2 with a treatment paradigm of 26 mg TEP daily for 54 days will start.
Subjects eligible for participation are subjects with newly diagnosed (within last 12 month) early-to-mild dementia due to AD and healthy volunteers who fulfill all inclusion criteria and have none of the exclusion criteria present at screening.
| Study group | Role | What they receive |
|---|---|---|
| Group 1a: TEP 26 mg daily for 4d | Experimental | Not described Receives: Drug: TEP |
| Group 1b: TEP 52 mg daily for 4d | Experimental | Not described Receives: Drug: TEP |
| Group 2: TEP 26 mg daily for 54d | Experimental | Not described Receives: Drug: TEP |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efflux of Amyloid beta peptides (Group mean changes from baseline)
To demonstrate a significantly increased efflux of Amyloid beta peptides from the brain into the bloodstream in subjects with newly diagnosed (within last 12 month) early-to-mild dementia due to Alzheimer's Disease vs. healthy volunteers that is expected to be caused by the ABCC1 transporter-stimulating effect of thiethylperazine.
Measured: Gr. 1a: up to 10 days; Gr.1b / 2: up tp 84 days
Secondary outcomes (3)
Scores obtained in psychometric tests [Cognition]
Changes in scores obtained in psychometric tests in newly diagnosed (within last 12 month) subjects with early-to-mild dementia due to AD vs. healthy volunteers as well as the analysis of their changes from baseline will be determined after treatment with thiethylperazine.
Measured: Group 1a and 1b and Group 2 on day 1, day 10 (Groups 1a/b) day 14 (Group 2) and day 84 (End of Trial-Group 1b/2).
Incidence of Treatment-Emergent Adverse Events [Safety and tolerability]
To assess the safety and tolerability of thiethylperazine in newly diagnosed (within last 12 month) subjects with early-to-mild dementia due to AD and to compare this profile with the outcome of a control group of healthy volunteers
Assessments:
Treatment-emergent Adverse Events (AEs) Treatment-emergent Serious Adverse Events (SAEs) Adverse Events leading to premature discontinuation of trial medication
Measured: Gr. 1a: up to 10 days; Gr.1b / 2: up tp 84 days
Cerebrospinal fluid (CSF) levels of Tau
To investigate the effect of thiethylperazine on CSF levels of phosphoTau181 and total Tau in subjects with newly diagnosed (within last 12 month) early-to-mild dementia due to AD
Measured: Gr. 1a: up to 10 days; Gr.1b / 2: up tp 84 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2018
- Study start24 Nov 2017
- Primary completion12 Jul 2021
- Study completion22 Oct 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Immungenetics AG
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Lutz Frölich, Prof. Dr., Principal investigator, Zentralinstitut für seelische Gesundheit, Medizinische Fakultät Mannheim, Universität Heidelberg,
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03417986
- Sponsor's protocol ID
- IMU-AD-001
- Acronym
- drainAD
- Status last verified
- Feb 2023
- First submitted
- 29 Nov 2017
- Last updated
- 22 Feb 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Ruoff LK, Banfer IWH, Liedtke DE, China SE, Wiltfang J, Bayer TA, Bock SF, Spandau F, Bouter C, Beindorff N, Bouter Y. Long-term thiethylperazine treatment in the Tg4-42 mouse model of Alzheimer's disease mouse: Therapeutic potential vs. adverse effects. Pharmacol Biochem Behav. 2026 Jan;258:174127. doi: 10.1016/j.pbb.2025.174127. Epub 2025 Nov 9.
PubMed 41218709
Study at a glance
From the registry record, last updated by the sponsor on 22 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Multicenter, Controlled Pharmaco-dynamic Clinical Trial to Explore the the Amyloid Beta Draining Effect of Thiethylperazine (TEP) in Subjects With Newly Diagnosed Early-to-mild Dementia Due to Alzheimer's Disease in Comparison to Healthy Volunteers
- ClinicalTrials.gov ID
- NCT03417986
- Acronym / sponsor ID
- drainAD / IMU-AD-001
- Conditions
- Alzheimer Disease
- Keywords
- Thiethylperazine, Alzheimer Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Immungenetics AGIndustry (pharma, biotech, devices)
- Study start
- 24 Nov 2017 (actual)
- Primary completion
- 12 Jul 2021 (actual)
- Study completion
- 22 Oct 2021 (actual)
- First posted
- 31 Jan 2018 (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.
This proof-of-mechanism clinical trial study will test the efficacy and safety of thiethylperazine (TEP) in subjects with early onset of Alzheimer's Disease (AD). There is a strong scientific rationale for this study: TEP is a very well-known substance that has been available since 1961 and approved for the prevention and treatment of nausea, vomiting as well as vertigo. Therefore, it has a well understood pharmacologic background and promising safety data. Using AD mouse models, it has been recently discovered and confirmed that TEP promotes transport of toxic Aβ from the brain into the blood. More importantly, it has also been demonstrated to improve learning deficits in mice. The striking biological effect of TEP in preclinical testing and its known safety and toxicity profile encourages the investigators to investigate this in a multicenter clinical trial in subjects with early-to-mild AD in comparison to healthy volunteers. The investigators will assess whether TEP is able to enhance the transport of Aβ peptides from the brain into the blood in subjects with early-to-mild AD and improves cognitive efficacy.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group 1a: TEP 26 mg daily for 4d | Experimental | Drug: TEP |
| Group 1b: TEP 52 mg daily for 4d | Experimental | Drug: TEP |
| Group 2: TEP 26 mg daily for 54d | Experimental | Drug: TEP |
Who may qualify
- Ages
- 55 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- For AD subject
- Newly diagnosed (< 12 months) early-to-mild Alzheimer's disease as classified by a Mini-Mental State Examination (MMSE) Score of 25-18 reconfirmed at screening
- AD diagnosis confirmed by recommended examinations in accordance with German DGN (Deutsche Gesellschaft für Neurologie)/DGPPN (Deutsche Gesellschaft für Psychiatrie und Psychotherapie,Psychosomatik und Nervenheilkunde) S3 Guideline "Dementia" and to standard at the clinical unit by:
- AD subject has full legal competence according to investigator opinion
- Ability to comply with requirements or cognitive and other testing for the entire length of the trial available
Key exclusion criteria (25 listed)
- CSF cut-off values identified during routine Neurochemical Dementia Diagnostics
- History or evidence of other significant neurological disease of the Central Nervous System (such as Parkinson's disease, multi-infarct dementia, fronto-temporal dementia, Huntington's disease, normal pressure hydrocephalus, brain tumor, progressive supra nuclear palsy, epilepsy, myasthenia gravis, subdural hematoma or multiple sclerosis)
- History of significant head trauma followed by persistent neurologic defaults or known structural brain abnormalities
- Significant neuroimaging abnormalities, previously known or discovered on the MRI scan, including evidence of infection, infarction (> 3 mm in size), brain tumors (other than small meningiomas), or other focal lesions, multiple lacunas or lacunas in a critical memory structure or severe confluent microvascular disease (but not mild white matter changes, which are frequent with aging)
- History or evidence of moderate congestive heart failure defined by the New York Heart Association criteria (class I-IV)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TEPAlso: ThiethylperazineFor safety reasons the clinical trial will first enroll 14 subjects (7 patients and 7 healthy volunteers) for Group 1a receiving 26 mg TEP daily for 4 days with subsequent safety evaluation, based on adverse events and the safety parameters discussed in the protocol. A second set of patients (Group 1b), which will receive a higher dosage of 52 mg per day for 4 days will be enrolled optionally after recommendation to continue and subsequently treatment Group 2 with a treatment paradigm of 26 mg TEP daily for 54 days will start. Subjects eligible for participation are subjects with newly diagnosed (within last 12 month) early-to-mild dementia due to AD and healthy volunteers who fulfill all inclusion criteria and have none of the exclusion criteria present at screening. | Drug | Group 1a: TEP 26 mg daily for 4d, Group 1b: TEP 52 mg daily for 4d, Group 2: TEP 26 mg daily for 54d |
Primary outcome
Efflux of Amyloid beta peptides (Group mean changes from baseline)
Time frame: Gr. 1a: up to 10 days; Gr.1b / 2: up tp 84 days
To demonstrate a significantly increased efflux of Amyloid beta peptides from the brain into the bloodstream in subjects with newly diagnosed (within last 12 month) early-to-mild dementia due to Alzheimer's Disease vs. healthy volunteers that is expected to be caused by the ABCC1 transporter-stimulating effect of thiethylperazine.
3 secondary outcomes
Scores obtained in psychometric tests [Cognition]
Time frame: Group 1a and 1b and Group 2 on day 1, day 10 (Groups 1a/b) day 14 (Group 2) and day 84 (End of Trial-Group 1b/2).
Incidence of Treatment-Emergent Adverse Events [Safety and tolerability]
Time frame: Gr. 1a: up to 10 days; Gr.1b / 2: up tp 84 days
Cerebrospinal fluid (CSF) levels of Tau
Time frame: Gr. 1a: up to 10 days; Gr.1b / 2: up tp 84 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Feb 2023.
- Derived from this study: PubMed 41218709Ruoff LK, Banfer IWH, Liedtke DE, China SE, Wiltfang J, Bayer TA, Bock SF, Spandau F, Bouter C, Beindorff N, Bouter Y. Long-term thiethylperazine treatment in the Tg4-42 mouse model of Alzheimer's disease mouse: Therapeutic potential vs. adverse effects. Pharmacol Biochem Behav. 2026 Jan;258:174127. doi: 10.1016/j.pbb.2025.174127. Epub 2025 Nov 9.
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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.
Lutz Frölich, Prof. Dr. principal investigator
Zentralinstitut für seelische Gesundheit, Medizinische Fakultät Mannheim, Universität Heidelberg,
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing TEP in people with Alzheimer Disease, run by Immungenetics AG at 2 sites in Germany.
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 18 inclusion and 25 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: finished, as of the sponsor's last update on 22 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Germany. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efflux of Amyloid beta peptides (Group mean changes from baseline) (time frame: Gr. 1a: up to 10 days; Gr.1b / 2: up tp 84 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03417986, which also lists 1 linked publication.
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 22 Feb 2023.