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Endothelial Facilitation in Alzheimer's Disease

Primary Purpose

Alzheimer's Disease

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Simvastatin
L-Arginine
Tetrahydrobiopterin
Sponsored by
University of Massachusetts, Worcester
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alzheimer's Disease focused on measuring Early Alzheimer, Mild Cognitive Impairment, Drug treatment, Cerebral blood flow, Endothelial facilitation, Cognitive improvement

Eligibility Criteria

55 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Subjects must have mild Alzheimer's Disease or Mild Cognitive Impairment (MCI);
  • age between 55-85;
  • Mini Mental Status Exam (MMSE) between 15-26;
  • a caregiver who can provide information, and bring patient to the sessions;
  • no known allergies to any of the medications to be used;
  • normal renal function; willingness of patient and spouse/responsible caregiver to participate.

Exclusion Criteria:

  • Significant Psychiatric disorder;
  • stroke; current use of any of the test medications (e.g., statin, L-Arginine, Kuvan);
  • phenylketonuria (PKU) ;
  • elevated serum phenylalanine level (>10 mg/dL);
  • allergy to any of the medications; current active malignancy;
  • renal insufficiency (elevated creatinine above 1.3mg/dl);
  • abnormal liver function (Alanine Aminotransferase (ALT) or Aspartate Transaminase (AST) 2x normal);
  • other serious disease including coronary insufficiency or congestive heart failure, carotid stenosis greater than 50%, active peptic ulcer, urinary tract or other active infection, cancer (except skin cancer, or 5 years inactive breast or prostate cancer )etc.;
  • pregnancy; or
  • inability to come to UMass for follow-up. Subjects may continue to take anticholinesterase drugs for Alzheimer's Disease (Aricept, Exelon, Razadyne) and/or Namenda, if they have been on the drug(s) for at least 3 months. Subjects on levodopa and male subjects taking drugs for erectile dysfunction (Viagra, Cialis, Levitra) are cautioned regarding hypotension.

Sites / Locations

  • UMass Medical School/ UMass Memorial Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Simvastatin + L-Arginine + Tetrahydrobiopterin

Arm Description

Simvastatin, 40 mg per day orally; L-Arginine, 2 Gm four times per day orally; Tetrahydrobiopterin 20 mg/kg/day orally

Outcomes

Primary Outcome Measures

Mean Change in Cerebral Blood Flow as Measured by Magnetic Resonance Imaging (MRI)
Measurement of changes to cerebral blood flow (ml/110g/min) in regions of interest as measured using Magnetic Resonance Imaging (MRI)
Change in Cerebral Blood Flow as Measured by Arterial Spin Labeling During Magnetic Resonance Imaging (MRI)
Data not available as files corrupted and could not be analyzed

Secondary Outcome Measures

Mini Mental State Examination (MMSE) Scores
Change in mental state as reflected by changes to mean Mini Mental State Examination (MMSE) score as measured 4 weeks, 8 weeks and 16 weeks post-baseline. The MMSE uses a 30 point questionnaire to measure cognitive impairment. The MMSE is scored from 0 to 30,with a score equal to or greater than 24 points indicating normal cognition, a score of 19-23 points indicating mild cognitive impairment, 10-18 points indicating moderate impairment and a score equal to or below 9 indicating severe impairment.
Cognitive Assessment Screening Test (CAST)
This outcome measured the change in average Cognitive Assessment Screening Test (CAST) scores for the participant group. The CAST is scored from 0 to 40. A higher score indicates better performance, and a lower score indicates worse performance. The participants were given the CAST at baseline, 4 weeks, 8 weeks and 16 weeks post-baseline. The outcome reports on the averaged change for the averaged CAST scores from baseline to 16 weeks.
Clinical Dementia Rating Scale (CDR)
This outcome measures Clinical Dementia Rating Scale (CDR) scores at baseline (enrollment) and 16 weeks post-enrollment. The Clinical Dementia Rating Scale is scored with a composite scale of 0 to 3, with higher scores indicating lower functional status and lower scores indicating better functional status.
Alzheimer's Disease Assessment Scale: Cognitive and Modified Version (ADAS-COG)
Mean Alzheimer's Disease Assessment Scale: Cognitive Subscale (ADAS-COG) score at baseline and at 16 weeks post-enrollment. The ADAS-COG consists of 11 tasks measuring disturbances of memory, language, praxis, attention and other cognitive abilities. Total scores range from 0 to 70, with higher scores (18 and above) indicating greater cognitive impairment.
Clinical Interview Based Impression of Change + Caregiver Input (CIBIC Plus)
The Clinical Interview Based Impression of Change + Caregiver Input (CIBIC Plus) is a semi-structured instrument to examine four major areas of patient function: General, Cognitive, Behavioral and Activities of Daily Living. It is scored from 1 to 7. A score of 1 indicates marked improvement, 4 indicates no change and 7 indicates marked worsening.

Full Information

First Posted
September 16, 2011
Last Updated
July 11, 2019
Sponsor
University of Massachusetts, Worcester
Collaborators
The Glass Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT01439555
Brief Title
Endothelial Facilitation in Alzheimer's Disease
Official Title
Endothelial Facilitation in Alzheimer's Disease. An Open Label Pilot Study of the Sequential and Cumulative Effects of Simvastatin, L-Arginine, and Sapropterin (Kuvan) on Cerebral Blood Flow and Cognitive Function in Patients With Alzheimer's Disease.
Study Type
Interventional

2. Study Status

Record Verification Date
July 2019
Overall Recruitment Status
Completed
Study Start Date
November 2011 (undefined)
Primary Completion Date
November 2017 (Actual)
Study Completion Date
November 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Massachusetts, Worcester
Collaborators
The Glass Foundation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No

5. Study Description

Brief Summary
Purpose of the study: Patients with mild Alzheimer's Disease will be given three different drugs over a 4-month period to try to increase the blood flow to their brains, and improve blood vessel and brain function. Each drug can help to open the blood vessels in the brain, and together they may be more effective than each drug alone. The hypothesis is that small blood vessels secrete substances that maintain the integrity of the brain, and may prevent loss of nerve cells leading to Alzheimer's Disease

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer's Disease
Keywords
Early Alzheimer, Mild Cognitive Impairment, Drug treatment, Cerebral blood flow, Endothelial facilitation, Cognitive improvement

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
11 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Simvastatin + L-Arginine + Tetrahydrobiopterin
Arm Type
Experimental
Arm Description
Simvastatin, 40 mg per day orally; L-Arginine, 2 Gm four times per day orally; Tetrahydrobiopterin 20 mg/kg/day orally
Intervention Type
Drug
Intervention Name(s)
Simvastatin
Other Intervention Name(s)
Tetrahydrobiopterin
Intervention Description
Simvastatin, 40 mg per day orally
Intervention Type
Drug
Intervention Name(s)
L-Arginine
Intervention Description
L-Arginine, 2 Gm four times per day orally;
Intervention Type
Drug
Intervention Name(s)
Tetrahydrobiopterin
Other Intervention Name(s)
Kuvan, Sapropterin
Intervention Description
Tetrahydrobiopterin 20 mg/kg/day orally
Primary Outcome Measure Information:
Title
Mean Change in Cerebral Blood Flow as Measured by Magnetic Resonance Imaging (MRI)
Description
Measurement of changes to cerebral blood flow (ml/110g/min) in regions of interest as measured using Magnetic Resonance Imaging (MRI)
Time Frame
Baseline to 16 weeks
Title
Change in Cerebral Blood Flow as Measured by Arterial Spin Labeling During Magnetic Resonance Imaging (MRI)
Description
Data not available as files corrupted and could not be analyzed
Time Frame
Baseline to week 16
Secondary Outcome Measure Information:
Title
Mini Mental State Examination (MMSE) Scores
Description
Change in mental state as reflected by changes to mean Mini Mental State Examination (MMSE) score as measured 4 weeks, 8 weeks and 16 weeks post-baseline. The MMSE uses a 30 point questionnaire to measure cognitive impairment. The MMSE is scored from 0 to 30,with a score equal to or greater than 24 points indicating normal cognition, a score of 19-23 points indicating mild cognitive impairment, 10-18 points indicating moderate impairment and a score equal to or below 9 indicating severe impairment.
Time Frame
Baseline to 4 weeks, 8 weeks and 16 weeks post-baseline
Title
Cognitive Assessment Screening Test (CAST)
Description
This outcome measured the change in average Cognitive Assessment Screening Test (CAST) scores for the participant group. The CAST is scored from 0 to 40. A higher score indicates better performance, and a lower score indicates worse performance. The participants were given the CAST at baseline, 4 weeks, 8 weeks and 16 weeks post-baseline. The outcome reports on the averaged change for the averaged CAST scores from baseline to 16 weeks.
Time Frame
Baseline to 16 weeks post-baseline
Title
Clinical Dementia Rating Scale (CDR)
Description
This outcome measures Clinical Dementia Rating Scale (CDR) scores at baseline (enrollment) and 16 weeks post-enrollment. The Clinical Dementia Rating Scale is scored with a composite scale of 0 to 3, with higher scores indicating lower functional status and lower scores indicating better functional status.
Time Frame
Baseline to 16 weeks post-baseline
Title
Alzheimer's Disease Assessment Scale: Cognitive and Modified Version (ADAS-COG)
Description
Mean Alzheimer's Disease Assessment Scale: Cognitive Subscale (ADAS-COG) score at baseline and at 16 weeks post-enrollment. The ADAS-COG consists of 11 tasks measuring disturbances of memory, language, praxis, attention and other cognitive abilities. Total scores range from 0 to 70, with higher scores (18 and above) indicating greater cognitive impairment.
Time Frame
Baseline to 16 weeks post-baseline
Title
Clinical Interview Based Impression of Change + Caregiver Input (CIBIC Plus)
Description
The Clinical Interview Based Impression of Change + Caregiver Input (CIBIC Plus) is a semi-structured instrument to examine four major areas of patient function: General, Cognitive, Behavioral and Activities of Daily Living. It is scored from 1 to 7. A score of 1 indicates marked improvement, 4 indicates no change and 7 indicates marked worsening.
Time Frame
Baseline to 4 weeks, 8 weeks and 16 weeks post-baseline

10. Eligibility

Sex
All
Minimum Age & Unit of Time
55 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subjects must have mild Alzheimer's Disease or Mild Cognitive Impairment (MCI); age between 55-85; Mini Mental Status Exam (MMSE) between 15-26; a caregiver who can provide information, and bring patient to the sessions; no known allergies to any of the medications to be used; normal renal function; willingness of patient and spouse/responsible caregiver to participate. Exclusion Criteria: Significant Psychiatric disorder; stroke; current use of any of the test medications (e.g., statin, L-Arginine, Kuvan); phenylketonuria (PKU) ; elevated serum phenylalanine level (>10 mg/dL); allergy to any of the medications; current active malignancy; renal insufficiency (elevated creatinine above 1.3mg/dl); abnormal liver function (Alanine Aminotransferase (ALT) or Aspartate Transaminase (AST) 2x normal); other serious disease including coronary insufficiency or congestive heart failure, carotid stenosis greater than 50%, active peptic ulcer, urinary tract or other active infection, cancer (except skin cancer, or 5 years inactive breast or prostate cancer )etc.; pregnancy; or inability to come to UMass for follow-up. Subjects may continue to take anticholinesterase drugs for Alzheimer's Disease (Aricept, Exelon, Razadyne) and/or Namenda, if they have been on the drug(s) for at least 3 months. Subjects on levodopa and male subjects taking drugs for erectile dysfunction (Viagra, Cialis, Levitra) are cautioned regarding hypotension.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Elizabeth R DeGrush, DO
Organizational Affiliation
UMass Medical School
Official's Role
Principal Investigator
Facility Information:
Facility Name
UMass Medical School/ UMass Memorial Medical Center
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01655
Country
United States

12. IPD Sharing Statement

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Endothelial Facilitation in Alzheimer's Disease

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