Patients with mild cognitive impairment of Alzheimer type or early Alzheimer dementia. MedDRA version: 19.0 Level: PT Classification code 10074616 Term: Prodromal Alzheimer's disease System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Trade Name: Sativex®
Pharmaceutical Form: Oromucosal spray
INN or Proposed INN: CANNABIDIOL
CAS Number: 13956-29-1
Other descriptive name: CANNABIDIOL
Concentration unit: mg/ml milligram(s)/millilitre
Sponsors
Centro de Investigación Biomédica en Red, Enfermedades Neurodegenerativas (CIBERNED)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: -Men and women (without childbearing potential) aged = 85 years (patients out of this range could be included after a previous assessment by the Investigator and approval by the Sponsor). 2. Diagnosis of probable Alzheimer’s disease (AD) dementia or MCI due to AD according to the diagnostic guidelines of the National Institute on Aging-Alzheimer’s Association workgroups. 3. Prodromal or early stage of AD according to the scores in the Global Deterioration Scale (3-4) and Mini Mental State Examination (MMSE) (>20). 4. Evidence of the AD pathophysiological process indicated by decreased levels of amyloid (450 pg/mL) or p-tau (> 50 pg/mL/mL) in CSF. 5. A baseline MRI study corroborating the clinical diagnosis (diffuse brain atrophy predominating in midtemporal and frontal regions) and excluding other potential causes of dementia, especially cerebrovascular lesions. 6. A baseline lumbar puncture with low levels of Aß (total or Aß42) and high levels of tau (total or phosphorylated) in CSF and acceptance of another lumbar puncture at the end of the treatment period. 7. Modified Hachinsky ischemic score equal or below 4. 8. Education for more than 8 years. 9. Female patients must be either surgically sterilized, at least 1-year postmenopausal or using adequate birth control. 10. Caregiver available living in the same household or interacting with patient at least 4 times a week, able to provide information about patient’s physical and behavioral symptoms and changes. 11. Patients living at home or old people’s home without continuous nursing care. 12. Good general health, hydration and nutrition status for participating in a 6-month clinical trial. 13. Treatment with anticholinesterasic agents or memantine will be allowed but it must be stable and well tolerated for at least 3 months. These treatments cannot be started or up titrated during all the duration of the trial. 14. SSRIs as antidepressants and benzodiazepines as anxiolytics or sleep inductors are permitted after maintenance of dose for three months prior to baseline evaluations. 15. Stable pharmacological treatment of any other chronic condition for at least one month prior to screening. 16. Signed informed consent by patient and caregiver prior to the initiation of any study specific procedure. 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 10 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
Exclusion criteria: 1. Failure to perform screening or baseline examinations. 2. Hospitalization or change of concomitant medication 1 month prior to screening or during screening period. 3. Clinical, laboratory or neuroimaging findings consistent with: ? other primary degenerative dementia, (dementia with Lewy bodies, frontotemporal dementia, Huntington’s disease, Jakob-Creutzfeldt Disease, Down’s syndrome, …) ? other neurodegenerative condition (Parkinson’s disease, amyotrophic lateral sclerosis, …) ? cerebrovascular disease (major infarct, one strategic or multiple lacunar infarcts, extensive white matter lesions) ? other central nervous system diseases (severe head trauma, tumors, subdural hematoma or other space occupying processes, …) ? other infectious, metabolic or systemic diseases affecting central nervous system (syphilis, hypothyroidism, vitamin B12 or folate deficiency, serum electrolytes out of normal range, juvenile onset diabetes mellitus …) 4. A current DSM-IV diagnosis of major depression, schizophrenia or bipolar disorder. 5. Clinically significant, advanced or unstable disease that may interfere with primary or secondary variable evaluations, may bias the assessment of the clinical or mental status of the patient or put the patient at special risk, such as: ? epileptic seizures within the last 3 years ? hepatic or respiratory insufficiency ? renal insufficiency (serum creatinine >2mg/dl) ? heart disease (myocardial infarction, unstable angina, heart failure, cardiomyopathy within 6 months before screening) ? bradycardia (heart beat 95/min.) ? hypertension or hypotension requiring treatment with more than 2 drugs ? AV block (type II / Mobitz II and type III), congenital long QT syndrome, sinus node dysfunction or prolonged QTcB-interval (males >450 and females >470 msec) ? uncontrolled diabetes ? malignant tumors within the last 5 years ? metastases 6. Disability that may prevent the subject from completing all study requirements (e.g., blindness, deafness, severe language difficulty) 7. Women who are fertile and of child bearing potential. 8. Chronic daily drug intake of: ? acenocoumarol, warfarin or digitoxin ? antidepressants (other than SSRIs), neuroleptics (except quetiapine up to a max 25 mg/d, or risperidone up to a max 1 mg/d) or major sedatives ? antiepileptic drugs prescribed to control seizures ? systemic anticholinergics ? nootropics ? centrally active anti-hypertensive drugs (such as clonidine, ?-methyl DOPA, guanidine, guanfacine) ? opioid containing analgesics ? anti-inflammatory agents, corticosteroids or immunosuppressants 9. Suspected or known drug or alcohol abuse*. 10. Suspected or known allergy or intolerance to cannabis or any components of the study treatment. 11. Metallic implants or any other cause precluding the performance of brain MRI. 12. Enrolment in another investigational study or intake of investigational drug within the previous 3 months. 13. Any condition which in the opinion of the investigator makes the patient unsuitable for inclusion in the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •To evaluate the safety and tolerability of three doses of Sativex® administered for 26 weeks in patients with MCI of Alzheimer type or early Alzheimer dementia •To evaluate the efficacy of three doses of Sativex® administered for 26 weeks to reduce inflammatory markers in CSF of patients with MCI of Alzheimer type or early Alzheimer dementia.;Secondary Objective: •To evaluate the effect of three doses of Sativex® administered for 26 weeks on the change in MRI measures of atrophy from baseline to endpoint •To evaluate other clinical changes in these patients after administration of three doses of Sativex® for 26 weeks on: o cognition o patient daily functioning o behavior and depressive mood o overall clinical change o health related quality of life •To find out a clinical and biological dose effect of Sativex® and identify the best dose to be tested in a future phase III trial. Exploratory Objectives • To evaluate the effect of Sativex® on several CSF parameters related to the physiopathology of the disease (tau, phospho-tau and beta-amyloid). • To ascertain any interaction of treatment with variables such as gender, stage of the disease, brain atrophy, ApoE genotype, and biological markers, and their effect on cognitive, behavioral and functional response.;Primary end point(s): • Safety Endpoint: Number of treatment emergent adverse events (TEAEs) and patients with an incidence rate of = 5% TEAEs will be compared with those in the placebo group. • Efficacy Endpoint: The change from baseline in the inflammatory markers in CSF of patients in the 3 active groups will be compared with those in the placebo group.;Timepoint(s) of evaluation of this end point: Change from baseline in the inflammatory markers: V2, screening and V7, Final | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The change from Baseline of the 3 active study medication groups will be compared with the placebo group in: • MRI measures of brain atrophy • Alzheimer’s Disease Assessment Scale cognitive (ADAS-cog). • Mini Mental State Examination (MMSE) • Symbol Digit Modalities • Word fluency test • Logical Memory • Trail Making Test • Alzheimer’s Disease Cooperative Study Unit Activities of Daily Living (ADCS-ADL). • Neuropsychiatric Inventory (NPI) • Clinical Global Impression of Change (CGIC) • Clinical Global Impression of Severity (CGIS) • European Quality of life Instrument (EQ-5D) - A clinical and/or biological dose effect of Sativex® will be disclosed after analyzing trends and consistency of observed changes in the three active treatment groups and placebo.;Timepoint(s) of evaluation of this end point: MMSE: Vscreening , V3, V6 and V7. Word Fluency test: Screening, V3, V4, V6 and V7. Cognitive battery: V3, V6 and V7. Global Deterioration Scale: screening, V3 and V7. Neuropsychiatric Inventory: V3, V6 and V7. ADCS-ADL and Clinical Global Assesment: V3, V6 and V7 EuroQol questionnaire: V3, V4, V6 and V7. | — |
Countries
Spain
Contacts
Public ContactDepartamento de Ensayos Clínicos
Dynamic Science
Outcome results
None listed