ATP in Alzheimer Disease

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.

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.

Study Overview

• Status: Completed
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Drug: ADENOSINE TRIPHOSPHATE; Drug: PLACEBO

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08028
    • Fundacio ACE
  • Barcelona, Spain
    • Hospital Sanitas Cima

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 53 years to 83 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

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

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

Collaborators and Investigators

• Sponsor: Sara Varea
• Investigators: Principal Investigator: Mercè Boada Rovira, MD PhD, Fundació ACE. Barcelona Alzheimer Treatment and Research Center

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2014
• Primary Completion (Actual): February 1, 2016
• Study Completion (Actual): February 1, 2016

Study Registration Dates

• First Submitted: October 22, 2014
• First Submitted That Met QC Criteria: October 29, 2014
• First Posted (Estimate): October 31, 2014

Study Record Updates

• Last Update Posted (Actual): March 29, 2017
• Last Update Submitted That Met QC Criteria: March 28, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Alzheimer
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Vasodilator Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Purinergic Agents; Purinergic P1 Receptor Agonists; Purinergic Agonists; Adenosine
• Other Study ID Numbers: ECA4A