ATP in Alzheimer Disease

Study Overview
=================
Brief Summary
-----------------
To Check whether systemic treatment with ATP alters the profile of cerebral metabolism in patients with Alzheimer's disease using MRS techniques (Magnetic Resonance Spectroscopy) and adjust the infusion (minimum effective dose) that promotes this metabolic change.

Official Title
-----------------
Evaluating the Effectiveness of the Use of Intravenous Infusions of Adenosine Triphosphate (ATP) in Patients With Moderate Alzheimer's Disease and Severe: Double-blind Dose Finding Clinical Trial.

Conditions
-----------------
Alzheimer's Disease

Intervention / Treatment
-----------------
* Drug: ADENOSINE TRIPHOSPHATE
* Drug: PLACEBO


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 1. Men and women aged 55-85 years 2. Diagnosis of possible or probable Alzheimer disease according to NIA-AA 2011 criteria. 3. Global Deterioration Scale Stadium 5-6 / 15-5 Mini-mental State examination 4. The patient is living with a family as a primary caregiver or a caregiver trained to accompany adequate and all intervention and follow-up visits. Patient and caregiver knowledge of local languages sufficient. 5. The patient and caregiver willing to participate in the study. There is a high probability that patient and caregiver to complete the study. 6. The patient has no sensory deficits preventing evaluation. 7. The patient receives a stable Alzheimer Disease conventional medication. No change in treatment at least 90 days prior to selection. 8. The patient receives a conventional stable medication for possible comorbidities. No change in treatment at least 90 days prior to selection. 9. The subject or his legal representative give prior informed consent that includes genetic studies of Apolipoprotein E and rs11870474. Exclusion Criteria: 1. Concomitant severe neurological disease Alzheimer Disease. 2. Presence or history of psychiatric disorders with an emphasis on positive behavioral disorders associated with Alzheimer Disease (aggressiveness, agitation, delusions, hallucinations, anxiety). 3. Current Severe systemic disease that may prevent completion of the study. 4. History STROKE. 5. History of convulsions and use of anticonvulsants. 6. History of myocardial infarction, angina pectoris, cardiac arrhythmias and other serious cardiovascular disorders such as congestive heart failure, and valvular aneurysms. 7. Background Diabetes mellitus and / or pictures of hypoglycemia. 8. Uncontrolled hypertension (systolic> 160 mmHg and / or Diastolic> 95 mmHg). 9. Systemic hypotension (SBP <86 mmHg) or bradycardia (<50 beats per minute) 10. Bronchial Asthma History or lung diseases that cause bronchospasm or bronchoconstriction 11. Kidney failure (patients with medical restrictions or income parenteral intake of fluids). 12. Liver failure. 13. Respiratory failure (need supplemental oxygen supply) 14. Blood donation in the last 90 days or anemia (Hb <10g/dL) 15. Use connection (<30 days prior to screening) of antidepressants, sedatives and hypnotics. 16. Using Alzheimer Disease experimental drugs in the last 60 days prior to screening. 17. Women who are pregnant or fertile 18. Inadequate venous access to prevent parenteral administration of infusions.

Ages Eligible for Study
-----------------
Minimum Age: 55 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 24 hours infusion of ATP<br> | Drug: ADENOSINE TRIPHOSPHATE<br>* Infusion of 2.5g of ATP in 500 mL of saline solution. (IV)<br>* Other names: ATP;|
| Experimental: 6 hours infusion of ATP<br> | Drug: ADENOSINE TRIPHOSPHATE<br>* Infusion of 2.5g of ATP in 500 mL of saline solution. (IV)<br>* Other names: ATP;|
| Placebo Comparator: 24 hours infusion of placebo<br> | Drug: PLACEBO<br>* Infusion of 500 mL of saline solution. (IV)<br>|
| Placebo Comparator: 6 hours infusion of placebo<br> | Drug: PLACEBO<br>* Infusion of 500 mL of saline solution. (IV)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Detection of brain metabolic changes after ATP infusion by spectroscopy techniques (H + MRS) | Spectroscopy will be taken one hour after the infusion (7h for patients allocated to 6h arm and 25h in 24h infusion arm) | expected average of 7-25 hours post infusion | 
| Changes in Cogstate results | one hour after the infusion (7h for patients allocated to 6h arm and 25h in 24h infusion arm) | expected average of 7-25 hours post infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Cogstate results | The cogstate is a software used to evaluate cognitive impairment | 3 months compared to baseline. | 
| Changes in test Mini-Mental State Examination |  | 3 months compared to baseline. | 
| Changes in synaptic activity after treatment administration Neurological examination |  | post treatment or 3 months post baseline | 
| Electrocardiogram results |  | an expected average of 90 days | 
| adverse events |  | at 90 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Alzheimer