A Study to Evaluate Albumin and Immunoglobulin in Alzheimer's Disease

Alzheimer's Disease Clinical Trial

— AMBAR  

Official title:

A Multicenter, Randomized, Controlled Study To Evaluate The Efficacy and Safety of Short-Term Plasma Exchange Followed by Long-Term Plasmapheresis With Infusion of Human Albumin Combined With Intravenous Immunoglobulin In Patients With Mild-Moderate Alzheimer's Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01561053
• Other study ID #: IG1002
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: April 19, 2012
• Est. completion date: March 6, 2018

Study information

• Verified date: July 2019
• Source: Grifols Biologicals, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the changes in the cognitive, functional, behavioral and global domains based on the different applicable psychometric batteries and scales.

Description:

A clinical trial comprised of 350 subjects with probable mild to moderate Alzheimer's Disease (AD) will be conducted primarily to determine whether plasmapheresis with infusion of human albumin combined with intravenous immunoglobulin (IVIG) is able to modify patient's cognitive, functional, behavioral and global domains. There will be 3 treatment groups and 1 control group. The subjects will be randomized in a 1:1:1:1 proportion.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 347
• Est. completion date: March 6, 2018
• Est. primary completion date: March 6, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years to 85 Years

Eligibility

Main Inclusion Criteria:

1. Males or females between 55-85 years of age at the time of signing of the informed consent document.

2. A diagnosis of Alzheimer's disease (NINCDS-ADRDA criterion), and mini-mental status examination (MMSE) score between >/=18 and </=26.

3. Current stable treatment with acetylcholine esterase inhibitors (AChEIs) and/or memantine for the previous three months.

4. The patient and a close relative or the legal representative must read the patient information sheet, agree to participation in the trial, and then sign the informed consent document (the patient personally and the close relative/legal representative).

5. The patient must be able to follow the study protocol, receive the treatment in the established time period, and continue during the follow-up interval.

6. A brain computed axial tomography (CAT) or magnetic resonance imaging (MRI) study, obtained in the 12 months prior to recruitment, showing the absence of cerebrovascular disease, should be available. Nevertheless, it is mandatory to use the MRI obtained during the screening period to rule out any cerebrovascular disease.

7. A stable care taker must be available, and must attend the patient study visits.

Main Exclusion Criteria:

1. Any contraindication for plasma exchange due to behavioral disorders or abnormal coagulation parameters, such as for example:

• Hypocalcemia (Ca++ < 8.7 mg/dL)

• Thrombocytopenia (<100,000/µL)

• Fibrinogen <1.5 g/L

• Prothrombin time (Quick) p<60% versus control (international normalized ratio (INR) >1.5)

• Beta-blocker treatment and bradycardia <55/min

• Treatment with angiotension-converting enzyme inhibitors (ACEIs) (increased risk of allergic reactions)

2. Hemoglobin < 10 g/dL

3. Difficult venous access precluding plasma exchange.

4. A history of frequent adverse reactions (serious or otherwise) to blood products.

5. Hypersensitivity to albumin or allergies to any of the components of Albutein.

6. History of immunoglobulin A (IgA) deficiency.

7. Known allergies to Flebogamma DIF components such as sorbitol.

8. History of thromboembolic complications of intravenous immunoglobulins.

9. Plasma creatinine > 2 mg/dl.

10. Uncontrolled high blood pressure (systolic blood pressure of 160 mmHg or higher and/or diastolic blood pressure of 100 mmHg or higher despite treatment during the last 3 months).

11. Liver cirrhosis or any liver problem with glutamic pyruvic transaminase (GPT) > 2.5 x upper limit of normal (ULN), or bilirubin > 2 mg/dL.

12. Heart diseases, as evidenced by myocardial infarction, severe or unstable angina, or heart failure (New York Association Class II, III or IV) in the past 12 months.

13. Participation in other clinical trials, or the receipt of any other investigational drug in the three months prior to the start of the study.

14. Any condition complicating adherence to the study protocol (illness with less than one year of expected survival, known drug or alcohol abuse, etc.).

15. Pregnant or nursing women or women not using effective contraceptive methods for at least one month after plasma exchange.

16. Fewer than six years of education (exclusion criteria under medical criterion).

17. Less than three months with stable treatment for behavioral disorders or insomnia.

18. Patients being treated with anticoagulants or antiplatelet therapy (antiaggregants) should not be recruited in the study.

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease

Intervention

Biological:
• Albumin 5%
Therapeutic plasma exchange with human albumin 5%
• Albumin 20%
Low volume plasma exchange with human albumin 5%
• Immunoglobulin
Intravenous human immunoglobulin 5%

Locations

Country	Name	City	State
Spain	Fundació ACE	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital Vall d'Hebrón	Barcelona
Spain	Hospital Universitario de Burgos	Burgos
Spain	Hospital General de Elche	Elche	Alicante
Spain	Hospital Universitario del Vinalopó	Elche	Alicante
Spain	Hospital Universitario de Getafe	Getafe	Madrid
Spain	Parc Hospitalari Martí i Julià	Girona
Spain	Hospital Universitari de Bellvitge	Hospitalet de Llobregat	Barcelona
Spain	Hospital Universitari de Santa Maria	Lleida
Spain	Hospital Clínico San Carlos	Madrid
Spain	Hospital General Universitario Gregorio Marañón	Madrid
Spain	Hospital General de Catalunya	Sant Cugat Del Vallès	Barcelona
Spain	Hospital Universitario Nuestra Señora de Candelaria	Santa Cruz de Tenerife	Canary Islands
Spain	Hospital Universitari Mútua de Terrassa	Terrassa	Barcelona
Spain	Hospital Universitario Doctor Peset	Valencia
Spain	Hospital Universitario y Politécnico La Fe	Valencia
Spain	Hospital Viamed Montecanal	Zaragoza
United States	Bradenton Research Center, Inc.	Bradenton	Florida
United States	Roper St. Francis Healthcare	Charleston	South Carolina
United States	The Cleveland Clinic Foundation	Cleveland	Ohio
United States	Wesley Neurology Clinic	Cordova	Tennessee
United States	Neurology Specialists Inc	Dayton	Ohio
United States	iResearch Atlanta, LLC	Decatur	Georgia
United States	Quantum Laboratories	Deerfield Beach	Florida
United States	Mountain View Clinical Research, Inc	Denver	Colorado
United States	Galiz Research, LLC	Hialeah	Florida
United States	Largo Medical Center	Largo	Florida
United States	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	Mid-Atlantic Geriatric/ARC	Manchester	New Jersey
United States	Allied Biomedical Research Institute	Miami	Florida
United States	L&L Research Choices, Inc	Miami	Florida
United States	Miami Dade Medical Research Institute, LLC	Miami	Florida
United States	The NeuroCognitive Institute	Mount Arlington	New Jersey
United States	Neurology Associates of Osmond Beach	Ormond Beach	Florida
United States	PharmaSeek LLC (DMI Research)	Pinellas Park	Florida
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Northern California Research	Sacramento	California
United States	RTR Medical Group	Savannah	Georgia
United States	Howard University	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Instituto Grifols, S.A.	Grifols Biologicals, LLC

Countries where clinical trial is conducted

United States,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	ADAS-Cog Total Score (Changes From Baseline to 14 Months) in Patients With Baseline MMSE:22-26	ADAS-Cog total score as a change from baseline to 14 months in patients with baseline Mini-Mental State Examination (MMSE):22-26; The ADAS-Cog Scale is a questionnaire that assesses cognitive performance in 12 different domains. The domains are: word recall, commands, constructional praxis, delayed word-recall task, naming objects/figures, ideational praxis, orientation, word recognition, remembering test instructions, comprehension, word finding difficulty, and spoken language ability. The total score ranges from 0-80 where a higher score indicates more cognitive impairment.	Baseline and 14 months
Other	ADCS-ADL Total Score (Changes From Baseline to 14 Months) in Patients With Baseline MMSE:22-26	ADCS-ADL total score as a change from baseline to 14 months in patients with baseline Mini-Mental State Examination (MMSE):22-26; The ADCS-ADL comprises 23 questions covering a wide array of activities of daily living. Many of the activities begin with an assessment of whether that activity is relevant and then, if yes, follow with an assessment of the difficulty. The total score over all activities ranges from 0-78 where a higher score indicates more autonomy (better outcome).	Baseline and 14 months
Other	ADAS-Cog Total Score (Changes From Baseline to 14 Months) in Patients With Baseline MMSE:18-21	ADAS-Cog score as a change from baseline to 14 months in patients with baseline Mini-Mental State Examination (MMSE):18-21; The ADAS-Cog Scale is a questionnaire that assesses cognitive performance in 12 different domains. The domains are: word recall, commands, constructional praxis, delayed word-recall task, naming objects/figures, ideational praxis, orientation, word recognition, remembering test instructions, comprehension, word finding difficulty, and spoken language ability. The total score ranges from 0-80 where a higher score indicates more cognitive impairment	Baseline and 14 months
Other	ADCS-ADL Total Score (Changes From Baseline to 14 Months) in Patients With Baseline MMSE:18-21	ADCS-ADL total score as a change from baseline to 14 months in patients with baseline Mini-Mental State Examination (MMSE):18-21; The ADCS-ADL comprises 23 questions covering a wide array of activities of daily living. Many of the activities begin with an assessment of whether that activity is relevant and then, if yes, follow with an assessment of the difficulty. The total score over all activities ranges from 0-78 where a higher score indicates more autonomy (better outcome).	Baseline and 14 months
Primary	Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) Total Score (Changes From Baseline to 14 Months)	ADAS-Cog total score as a change from baseline to 14 months; The ADAS-Cog Scale is a questionnaire that assesses cognitive performance in 12 different domains. The domains are: word recall, commands, constructional praxis, delayed word-recall task, naming objects/figures, ideational praxis, orientation, word recognition, remembering test instructions, comprehension, word finding difficulty, and spoken language ability. The total score ranges from 0-80 where a higher score indicates more cognitive impairment.	Baseline and 14 months
Primary	Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) Total Score (Changes From Baseline to 14 Months)	ADCS-ADL total score as a change from baseline to 14 months; The ADCS-ADL comprises 23 questions covering a wide array of activities of daily living. Many of the activities begin with an assessment of whether that activity is relevant and then, if yes, follow with an assessment of the difficulty. The total score over all activities ranges from 0-78 where a higher score indicates more autonomy (better outcome).	Baseline and 14 Months