Endothelial Facilitation in Alzheimer's Disease

NCT01439555 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 13748
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

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

Conditions

Alzheimer's Disease

Keywords

Early Alzheimer; Mild Cognitive Impairment; Drug treatment; Cerebral blood flow; Endothelial facilitation; Cognitive improvement

Outcome Measures

Primary Outcomes (2)

• 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)

  Baseline to 16 weeks

• 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

  Baseline to week 16

Secondary Outcomes (5)

• Mini Mental State Examination (MMSE) Scores

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

• Cognitive Assessment Screening Test (CAST)

  Baseline to 16 weeks post-baseline

• Clinical Dementia Rating Scale (CDR)

  Baseline to 16 weeks post-baseline

• Alzheimer's Disease Assessment Scale: Cognitive and Modified Version (ADAS-COG)

  Baseline to 16 weeks post-baseline

• Clinical Interview Based Impression of Change + Caregiver Input (CIBIC Plus)

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

Study Arms (1)

Simvastatin + L-Arginine + Tetrahydrobiopterin

EXPERIMENTAL

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

Drug: Simvastatin; Drug: L-Arginine; Drug: Tetrahydrobiopterin

Interventions

Simvastatin DRUG

Simvastatin, 40 mg per day orally

Also known as: Tetrahydrobiopterin

Simvastatin + L-Arginine + Tetrahydrobiopterin

L-Arginine DRUG

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

Simvastatin + L-Arginine + Tetrahydrobiopterin

Tetrahydrobiopterin DRUG

Tetrahydrobiopterin 20 mg/kg/day orally

Also known as: Kuvan, Sapropterin

Simvastatin + L-Arginine + Tetrahydrobiopterin

Eligibility Criteria

• Age: 55 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Massachusetts, Worcester: lead
• The Glass Foundation: collaborator

Study Sites (1)

UMass Medical School/ UMass Memorial Medical Center

Worcester, Massachusetts, 01655, United States

Location

Related Publications (1)

• 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.

  PMID: 36115980 DERIVED

MeSH Terms

Conditions

Alzheimer Disease; Cognitive Dysfunction

Interventions

Simvastatin; sapropterin; Arginine

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Cognition Disorders

Intervention Hierarchy (Ancestors)

Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Amino Acids, Essential

Limitations and Caveats

The data for the MRI measurements (cerebral blood flow) experienced file corruption, rendering segments of data irretrievable and the whole set non-analyzable.

Results Point of Contact

• Title: Elizabeth DeGrush, DO
• Organization: UMass Medical School

elizabeth.degrush@umassmemorial.org

508-334-1000

Study Officials

• Elizabeth R DeGrush, DO

  UMass Medical School

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, Psychiatry

Study Record Dates

• First Submitted: September 16, 2011
• First Posted: September 23, 2011
• Study Start: November 1, 2011
• Primary Completion: November 1, 2017
• Study Completion: November 1, 2017
• Last Updated: July 30, 2019
• Results First Posted: July 30, 2019

Record last verified: 2019-07

Locations

US (1)