December 21, 2001 at 11:26 PM EST - Updated July 1 at 8:40 AM
CLEVELAND (AP) - A healthy volunteer died after drinking a mixture as part of an Alzheimer's disease study.
The researcher voluntarily ended the study after the death in May, and the policy was changed on the preparation of substances given to research subjects, The Plain Dealer reported Friday.
Elaine Jones Holden-Able, 70, a nurse from Warrensville Heights, died a month after she drank a mixture of methionine and orange juice prepared by an unlicensed dietary aide.
The aide, who had worked on research projects for more than 20 years, said she gave the woman the correct dose, but she admitted some confusion to investigators about how to convert milligrams to grams.
"Put all together, we can't rule out an overdose," said Eric Cottington, associate vice president for research at Case Western Reserve University.
Methionine is an essential amino acid commonly found in meat and milk and widely available in health food stores.
Studies have found that high levels of methionine are associated with cardiovascular disease. Alzheimer's patients also have elevated methionine levels, leading researchers to investigate whether a breakdown in how the body processes the amino acid points to a higher risk of getting the memory-robbing disease.
Dr. Robert Friedland, a University Hospitals neurologist, was studying how healthy "control" volunteers processed a one-time dose of methionine compared with Alzheimer's patients.
The study was being done under a grant from the Philip Morris tobacco company to Case Western. After some studies had suggested that nicotine might help prevent Alzheimer's, Philip Morris paid for the research as part of a wider investigation of the disease's risk factors.
The research was to involve 20 healthy volunteers and 20 Alzheimer's patients. Holden-Able was the second volunteer. The first participated without any problems, the newspaper said.
Earlier this month, federal regulators with the Office for Human Research Protections cleared University Hospitals, Case Western and their researchers of significant wrongdoing in the death.
The hospital now requires a licensed pharmacist to prepare all substances given to research subjects and requires the orders to be in writing.
Holden-Able drank the mixture at 8:32 a.m. on April 4 and began vomiting about 2½ hours later. By 4:55 p.m. she had become confused and combative and was moved to the emergency room, where she went into respiratory arrest. She died at University Hospitals 32 days later of acute respiratory distress syndrome.
Blood tests revealed that four hours after she drank the methionine mixture, the amino acid's level in her body was 144 times higher than normal.
"I don't know what a fatal dose is," said Dr. S. Harvey Mudd, a methionine expert at the National Institute of Mental Health in Bethesda, Md., and consultant in the investigation. "However, I have never heard of another situation quite like this. The methionine level was extraordinarily high."
An autopsy found nothing in the woman's health or background to explain the high levels, leading investigators to examine the dosage.
Holden-Able had an extensive nursing career in the Cleveland area and in Washington, D.C.
"She was a wonderful woman, a nurse who volunteered to take a substance that was not considered harmful," said John Scharon, a lawyer retained by the family. No suit has been filed.
(Copyright 2001 by The Associated Press. All Rights Reserved.)