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Alzheimer's DiseasePhase 2NCT01439555

Endothelial Facilitation in Alzheimer's Disease

A Phase 2 study testing Simvastatin, L-Arginine and Tetrahydrobiopterin in people with Alzheimer's Disease, run by University of Massachusetts, Worcester at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 55 to 85 years
Conditions the study is for
Alzheimer's Disease
What is being tested?
Simvastatin, L-Arginine and Tetrahydrobiopterin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
11 participants
Where
1 siteUnited States
Study dates
Nov 2011to Nov 2017
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 55 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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);
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  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • UMass Medical School/ UMass Memorial Medical Center

    Worcester, Massachusetts, 01655

Other trials in United States

About this study

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.

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

Being tested
Simvastatin, L-Arginine, Tetrahydrobiopterin
Keywords
Early Alzheimer, Mild Cognitive Impairment, Drug treatment, Cerebral blood flow, Endothelial facilitation, Cognitive improvement
Medical subject headings
Alzheimer Disease, Cognitive Dysfunction

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SimvastatinDrug

    Also called Tetrahydrobiopterin

    Simvastatin, 40 mg per day orally

  • L-ArginineDrug

    L-Arginine, 2 Gm four times per day orally;

  • TetrahydrobiopterinDrug

    Also called Kuvan, Sapropterin

    Tetrahydrobiopterin 20 mg/kg/day orally

Study groups in NCT01439555
Study groupRoleWhat they receive
Simvastatin + L-Arginine + TetrahydrobiopterinExperimentalSimvastatin, 40 mg per day orally; L-Arginine, 2 Gm four times per day orally; Tetrahydrobiopterin 20 mg/kg/day orally
Receives: Drug: Simvastatin; Drug: L-Arginine; Drug: Tetrahydrobiopterin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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)

    Measured: Baseline to 16 weeks

  2. 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

    Measured: Baseline to week 16

Secondary outcomes (5)

  1. 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.

    Measured: Baseline to 4 weeks, 8 weeks and 16 weeks post-baseline

  2. 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.

    Measured: Baseline to 16 weeks post-baseline

  3. 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.

    Measured: Baseline to 16 weeks post-baseline

  4. 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.

    Measured: Baseline to 16 weeks post-baseline

  5. 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.

    Measured: Baseline to 4 weeks, 8 weeks and 16 weeks post-baseline

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Sep 2011 (estimated)
  2. Study startNov 2011
  3. Primary completionNov 2017
  4. Study completionNov 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
11 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01439555
Sponsor's protocol ID
13748
Status last verified
Jul 2019
First submitted
16 Sep 2011
Last updated
30 Jul 2019
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Degrush E, Shazeeb MS, Drachman D, Vardar Z, Lindsay C, Gounis MJ, Henninger N. Cumulative effect of simvastatin, L-arginine, and tetrahydrobiopterin on cerebral blood flow and cognitive function in Alzheimer's disease. Alzheimers Res Ther. 2022 Sep 17;14(1):134. doi: 10.1186/s13195-022-01076-7.

    PubMed 36115980

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Simvastatin, L-Arginine and Tetrahydrobiopterin in people with Alzheimer's Disease, run by University of Massachusetts, Worcester at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Jul 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mean Change in Cerebral Blood Flow as Measured by Magnetic Resonance Imaging (MRI) (time frame: Baseline to 16 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01439555, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jul 2019.

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