Clinical trial: The Efficacy of a Combination Regimen in Patients With Mild to Moderate Probable Alzheimer's Disease (NCT01921972)

Eligibility criteria:
Inclusion Criteria:

          1. Willingness to participate, as indicated by written informed consent of the patient.
             The competence of the participating patient has to be assessed by a physician who is
             not involved in this trial.

          2. Male or postmenopausal female outpatients.

          3. Age of > 50 years at time of randomization.

          4. Diagnosis of probable Alzheimer's Disease (according to NINCDS-ADRDA criteria).

          5. Clinical and psychometric rating cut-off score (valid at randomisation): MMSE range of
             15 to 26 points.

          6. MRI brain scan not older than 12 months (before randomization) compatible with the
             diagnosis of Alzheimer's Disease. (The MRI brain scan must be repeated if older than
             12 months or if clinically indicated).

          7. Patient being ambulatory having adequate vision and hearing abilities to allow
             neuropsychological testing.

          8. Patient with a knowledgeable, cooperative, reliable caregiver/informant who is willing
             to follow the study procedure as indicated by written informed consent.

        Exclusion Criteria:

          1. Dementia of any other type than AD:

               1. vascular dementia

                    -  HIS Score (modified acc. to Rosen) > 5 or

                    -  evidence for VD acc. to NINCDS-AIREN criteria.

               2. depressive pseudodementia defined acc. to DSM-IV criteria for major depression.

               3. other non-AD dementia.

          2. Significant neurological disease other than AD, such as cerebral tumor, Huntington's
             disease, Parkinson's disease, normal pressure hydrocephalus, subdural hematoma, mental
             retardation, history of brain surgery or serious head trauma with residual deficits.

          3. Diagnosis of psychosis (requiring hospitalization or antipsychotic therapy for more
             than two weeks) within the past 10 years not associated with AD or a diagnosis of
             alcoholism or drug dependence within the past 10 years.

          4. History of epileptic seizures or patient receiving antiepileptic drugs.

          5. Abnormal laboratory test results considered clinically relevant for dementia: e.g.,
             electrolyte changes, folate deficiency, vitamin B12 deficiency, pathological thyroid
             function (T3 and TSH levels), positive syphilis serology.

          6. Patient who, in the opinion of the investigator, is suffering from an acute or poorly
             controlled illness, such as:

               1. Presently uncontrolled hypertension (> 180 mmHg systolic or > 100 mmHg
                  diastolic).

               2. Myocardial infarction within the last six months.

               3. Patient with uncompensated congestive heart failure (NYHA Class III or IV)

               4. Severe renal, hepatic or gastrointestinal disease, which could alter absorption,
                  metabolism or excretion of the trial drug.

               5. Serum creatinine > 130 μmol/l or 1.5 mg/dl, transaminases (ALAT, ASAT) or GGT >
                  twice the upper limit of normal range.

               6. Uncontrolled diabetes on entry into the double-blind phase of the research
                  project (fasting blood glucose > 10.0 mmol/l or 180 mg/dl in repeated tests) or
                  patient requiring insulin treatment.

          7. Patient taking any inadmissible medication, such as:

               -  Any investigational drug.

               -  Anticonvulsants (incl. barbiturates).

               -  Anti-Parkinson agents.

               -  Dopaminergic agents.

               -  Amantadine.

               -  Antimuscarinic agents (i. e., anticholinergics).

               -  Selegiline, MAOI.

          8. Any condition that precludes cooperation with the tests or other investigations during
             the study (e.g., seeing or hearing loss, relevant confusion or agitation,
             musculoskeletal disorders, contraindication for magnetic resonance imaging, i.e.,
             presence of pacemaker, metallic implants in high risk areas, presence of metallic
             material in high risk areas, history of claustrophobia. Hip implants are not
             contraindicated).

          9. Patient has participated in an investigational clinical trial during the last 2
             months.
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 50 Years old.


Patient description (medical language): A 70-year-old man comes to the office accompanied by his wife.  The patient has experienced progressive memory loss over the last years.  He needs help with some of his routine activities, such as paying bills.  The patient's wife says, "He used to be such an independent person, but now he needs help with many things, even finding direction to home!"  Medical history includes hypertension, hyperlipidemia, and type 2 diabetes mellitus.  Family history includes Alzheimer disease in his father.  MRI reveals diffuse cortical and hippocampal atrophy. The diagnosis of AD is made using the National Institute on Aging and the Alzheimer's Association (NIA-AA) criteria.

Patient description (patient's own words): I am a 70-year-old man, and I paid a visit to the doctor with my wife the other day. I noticed that I tend to forget small things and that my memory has decreased over the past few years. I even ask my wife to help me out with my daily routine. I used to be the one paying the bills, but now she has to give me a hand. My wife mentioned to the doctor that I used to be independent and that I tend to forget where we live. I suffer from hypertension, high cholesterol, and type 2 diabetes. My poor dad was suffering from Alzheimer disease, so I hope I'm not going to end the same way! I did an MRI and they found out that some part of my brain was decreasing. I also did an Alzheimer test.

Does the patient match the trial criteria? Entailment