Study to assess 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

Phase 1

• Conditions: ewly diagnosed early-to-mild dementia due to Alzheimer's Disease; MedDRA version: 20.0Level: PTClassification code 10012271Term: Dementia Alzheimer's typeSystem Organ Class: 10029205 - Nervous system disorders; Therapeutic area: Psychiatry and Psychology [F] - Mental Disorders [F03]

• Registration Number: EUCTR2014-000870-20-DE
• Lead Sponsor: Immungenetics AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2014-09-15
• Last Update Posted: 8 November 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 70

Inclusion Criteria

For AD subject only:
1.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
2.AD diagnosis confirmed by recommended examinations in accordance with German DGN/DGPPN S3 Guideline Dementia” and to standard at the clinical unit by:
-psychometric and cognitive tests
-lumbar puncture in subjects with uncertain AD diagnosis following 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 SD below age adjusted norms, according to hospital standard)
3.AD subject has full legal competence according to investigator opinion
4.Ability to comply with requirements or cognitive and other testing for the entire length of the trial available

For healthy volunteer:
5.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:
6.Age = 55 - = 75 years
7.Written informed consent to participate within this trial
8.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 receptor antagonists)
9.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.
10.Post-menopausal females (post menopausal amenorrhea for at least 2 years or surgically sterilized (hysterectomy), tubal ligation is not acceptable)
11.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 IUDs (intrauterine devices), or refrain from sexual intercourse during the trial and until 3 months after completion of the trial
12.Good general health with no additional disease states that could interfere with the trial due to the investigator’s assessment

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 70
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 70

Exclusion Criteria

1.CSF cut-off values identified during routine Neurochemical Dementia Diagnostics
2.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, pro-gressive supra nuclear palsy, epilepsy, myasthenia gravis, subdural hematoma or multiple sclerosis)
3.History of significant head trauma followed by persistent neurologic defaults or known structural brain abnormalities
4.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)
5.History or evidence of moderate congestive heart failure defined by the New York Heart Association criteria (class I-IV)
6.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)
7.History of new cardiovascular event within the last 6 months
8.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/min
9. Clinically significant renal disease or insufficiency, including but not limited to creatinine value of >1.5 mg/dl
10.ALT, AST, total bilirubin, or alkaline phosphatase >2.5 times the upper limit of normal laboratory range, or history of severe hepa-tobiliary disease (e.g. hepatitis B or C, or cirrhosis) without enzyme elevation
11.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
12.Positive tested for human immunodeficiency virus (HIV) at Screening Visit
13.Fasting triglycerides >2.5 times of the upper limit of normal
14.Uncontrolled diabetes (FBG > 150 mg/dl)
15.Coagulopathy or any kind of anti-coagulant therapy
16.Extrapyramidal syndrome
17.Elevation of prolactin, e.g. subject with prolactin-dependent breast cancer or pituitary tumor
18.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
19.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, ECT etc.)
20.Significant history of alcohol abuse or drug abuse within the past 6 months (at the judgment of the investigator)
21.Current treatment with TEP or treatment up to 24 month prior to screening
22.Known incompatibility of TEP or phenothiazines
23.Subject is receiving the following treatment that may interact with TEP, e.g. adrenaline, tricyclic antidepressants, narcotics, bromocriptine, MAO inhibitors, CYP2D6 inhibitors, tramadol, pentetrazol, levodopa, anticonvulsants, medication causing extrapyramidal symptoms increases the likelihood of central nervous system side effects
24.Participation in a clinical trial involving another investigational drug within 4 weeks prior to screening visit
25.Wom

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified