Clinical trial NCT00432081: Effect of Indomethacin on the Progression of Alzheimer's Disease
Official title: Effect of Indomethacin on the Progression of Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Alzheimer Disease
Keywords: Dementia
Inflammation
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Drug Therapy
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: American Health Assistance Foundation
name: Netherlands Brain Foundation
name: Netherlands Alzheimer Foundation
First posted: 2007-02-06
Enrollment: 160
Sex: ALL
Minimum age (years): 40
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Eligibility 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.

Primary outcomes:
measure: Score on the Cognitive subscale of the Alzheimer's Disease Assessment Scale at 12 months.
Secondary outcomes:
measure: Score on the Noncognitive subscale of the Alzheimer's Disease Assessment Scale at 12 months
measure: Score on the Clinician Interview-Based Impression of Change with caregiver input at 12 months
measure: Score on the Mini-Mental State Examination at 12 months
measure: Score on the Neuropsychiatric Inventory at 12 months
measure: Score on the The Interview for Deterioration in Daily living activities in Dementia at 12 months
measure: The occurrence of adverse events during 12 months of treatment
Other outcomes:
Locations:
city: Arnhem
country: Netherlands
facility: Rijnstate Hospital
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center
Study officials:
affiliation: Radboud University Medical Center Nijmegen
name: Rene WM Jansen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Radboud University Medical Center Nijmegen
name: Berry PH Kremer, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Radboud University Medical Center Nijmegen
name: Danielle De Jong, MD
role: STUDY_DIRECTOR
References:
citation: 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. doi: 10.1212/wnl.43.8.1609.
citation: McGeer PL, McGeer EG. NSAIDs and Alzheimer disease: epidemiological, animal model and clinical studies. Neurobiol Aging. 2007 May;28(5):639-47. doi: 10.1016/j.neurobiolaging.2006.03.013. Epub 2006 May 11.
citation: de Jong D, Jansen R, Hoefnagels W, Jellesma-Eggenkamp M, Verbeek M, Borm G, Kremer B. No effect of one-year treatment with indomethacin on Alzheimer's disease progression: a randomized controlled trial. PLoS One. 2008 Jan 23;3(1):e1475. doi: 10.1371/journal.pone.0001475.