Effect of Indomethacin on the Progression of Alzheimer's Disease

Condition(s) targeted: Alzheimer Disease

Intervention: indomethacin (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: Radboud University

Official(s) and/or principal investigator(s):
Rene WM Jansen, MD, PhD, Principal Investigator, Affiliation: Radboud University Medical Center Nijmegen
Berry PH Kremer, MD, PhD, Principal Investigator, Affiliation: Radboud University Medical Center Nijmegen
Danielle De Jong, MD, Study Director, Affiliation: Radboud University Medical Center Nijmegen

The purpose of this study is determine whether indomethacin is able to retard disease progression in patients with mild to moderate Alzheimer's disease.

Official title: Effect of Indomethacin on the Progression of Alzheimer's Disease

Study design: Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: Score on the Cognitive subscale of the Alzheimer’s Disease Assessment Scale at 12 months.

Secondary outcome:

Score on the Noncognitive subscale of the Alzheimer’s Disease Assessment Scale at 12 months

Score on the Clinician Interview-Based Impression of Change with caregiver input at 12 months

Score on the Mini-Mental State Examination at 12 months

Score on the Neuropsychiatric Inventory at 12 months

Score on the The Interview for Deterioration in Daily living activities in Dementia at 12 months

The occurrence of adverse events during 12 months of treatment

Detailed description: Previous research indicates that inflammation plays a role in the pathogenesis of Alzheimer’s disease (AD), and nonsteroidal anti-inflammatory drugs (NSAIDs) may retard the progression of the disease.

Comparison(s): Cognitive decline of patients with mild to moderate AD receiving the NSAID indomethacin, compared to cognitive decline of patients with mild to moderate AD receiving placebo, during a one-year period.

Minimum age: 40 Years. Maximum age: 90 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- The patient will satisfy the DSM-IV criteria for dementia of the Alzheimer’s type.

- The patient will satisfy the NINCDS/ADRDA criteria for the clinical diagnosis of

probable Alzheimer’s disease (Appendix I).

- The severity of dementia for each patient will be quantified by a Mini-Mental State

Examination (MMSE) score between 10 and 26 (both inclusive).

- The patient is living at home or in a home for the elderly.

- The patient has a responsible caregiver who is able to provide information about the

patient’s functional status.

- Written informed consent is obtained from the patient or the legally accepted

representative.

Exclusion Criteria:

- The patient satisfies the NINDS-AIREN criteria for probable vascular dementia.

- A known exaggerated pharmacological sensitivity or allergy to NSAID’s.

- History of peptic ulceration, gastric surgery or gastrointestinal bleeding.

- Current diagnosis of active peptic ulceration.

- Current diagnosis of severe and unstable cardiovascular disease.

- Current diagnosis of renal failure.

- Advanced, severe and unstable disease of any type, other than Alzheimer’s disease,

that may interfere with primary and secondary variable evaluations, including a medical condition which should be expected to progress, recur, or change to such an extent that it may bias the assessment of the clinical or mental status of the patient to a significant degree or put the patient at special risk.

- Intake of any of the following concomitant medications: salicylates, coumarin

derivatives, ACE-inhibitors, loop diuretics.

- Intake of any of the following concomitant medications more than two months

immediately prior or during the study: NSAID’s, systemic corticosteroids.

- Intake of any of the following concomitant medications with a possible effect on

cognition: estrogen, deprenyl, vitamin E, neuroleptics, anticholinergics. Patients using stable doses of cholinesterase inhibitors were eligible, with the provision that the dose should not be changed during the study. Cholinesterase inhibitors could not be initiated during the study.

- Excessive use of alcohol (more than 5 units per day)

- The patient is, either alone or with the aid of a caregiver, not able to reliably take

the medication.

Radboud University Medical Center, Nijmegen 6500 HB, Netherlands

Rijnstate Hospital, Arnhem 6800 TA, Netherlands

Related publications:

Rogers J, Kirby LC, Hempelman SR, Berry DL, McGeer PL, Kaszniak AW, Zalinski J, Cofield M, Mansukhani L, Willson P, et al. Clinical trial of indomethacin in Alzheimer's disease. Neurology. 1993 Aug;43(8):1609-11.

McGeer PL, McGeer EG. NSAIDs and Alzheimer disease: Epidemiological, animal model and clinical studies. Neurobiol Aging. 2006 May 10; [Epub ahead of print]

Starting date: May 2000
Ending date: August 2005
Last updated: February 5, 2007