Alzheimer's DiseasePhase 2NCT00001662
Treatment of Alzheimer's Disease With CX516 (Ampalex)
A Phase 2 study testing CX516 (Ampalex) in people with Alzheimer's Disease and Dementia, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial summary
Glutamate is an amino acid released by brain cells that acts to excite other cells. Glutamate attaches to special sites on cells called AMPA (alpha-amino-2,3-dihydro-5 methyl 3-oxo-4-isoxazolepropanoic acid) receptors. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Alzheimer's Disease, Dementia
- What is being tested?
- CX516 (Ampalex)
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 1996to Nov 2005
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Study subjects will satisfy NINCDS-ADRDA criteria for probable Alzheimer's disease.
- Dementia severity will be mild to moderate range with Mini-Mental Status Examination total score between 12 and 26, inclusive.
- The modified Hachinski Ischemia Score must be less than 4, and brain MRI performed within 15 months of enrollment must be compatible with the diagnosis of Alzheimer's disease.
- Dementia must be present historically for at least one year. Baseline electroencephalogram must not show significant epileptiform features.
- Study subjects will show deficits in at least two cognitive spheres, including memory.
- Modified Hachinski Ischemia Score must be less than 4, and Folstein mini-mental status examination total score must be between 12 and 26.
Show all 16Show fewer
- Cognitive difficulties must e present historically for at least one year.
- Brain MRI performed with 15 months of enrollment must be normal or show atrophy.
- Baseline electroencephalogram must not show epileptiform features.
- In addition, all patients must have acceptable nutritional status.
- Patients must be between ages 40 and 85.
- Patients must be sterile, post-menopausal, or using an acceptable forms of birth control.
- Chest x-ray within 15 months before enrollment must be acceptable for the trial.
- Participants in this study will reflect the diversity of those suffering from dementia.
- No one will be excluded or discriminated against based on the grounds of race, creed, or gender.
- Every attempt will be made to include women and minorities in the study population.
Who cannot join
- Hemispheric stroke, hydrocephalus, subdural hematoma, or mass lesion on neuroimaging study; "epileptiform" baseline EEG or known seizure disorder; head trauma with loss of consciousness concurrent with onset of dementia; chronic CNS infection (positive MHA-TP or FTA-ABS acceptable if luetic brain disease excluded by documented studies or treatment).
- Acute serious infection, including hepatitis; hypothyroidism (TSH greater than 6.0 microunits/mL); folic acid deficiency (less than 0.9 ng/mL); vitamin B12 deficiency (less than 160 pg/mL) within one year prior to enrollment; severe renal insufficiency (creatinine clearance less than 25 mL/min, BUN greater than 40 mg/dL, or serum creatinine greater than 2.0 mg/dL); hepatic insufficiency (SGPT or SGOT greater than 3 x upper limit of normal, or total bilirubin greater than 2.0 mg/dL). Due to the serious adverse event transient agranulocytosis report in another study of CX516, patients will neutropenia or low normal white blood cell counts (greater than or equal to 3.5 K/microliter) will be excluded from this study.
- PSYCHIATRIC:
- Depression if present during screening. Depression will be diagnosed clinically and with depression rating scale(s), such as Hamilton Depression Rating Scale, if needed.
- PREVIOUS AND CONCOMITANT MEDICATIONS:
- Administration of tacrine, donepezil, rivastigmine, galantamine, anti-depressants are prohibited within thirty days prior to enrollment.
- OTHER CONDITIONS:
- Any hepatic, cardiovascular, gastrointestinal, or hematological illness which could interfere with drug absorption, distribution, metabolism, or excretion; known hypersensitivity to CX516 or its vehicle; inability to swallow tablets or to comply with medication schedule; no significant care giver; uncorrectable loss of hearing or eyesight that precludes psychometric testing; inability to comprehend instructions or to respond to test items.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institute of Neurological Disorders and Stroke (NINDS)
Bethesda, Maryland, 20892
About this study
Official title: Tolerability and Primary Efficacy of CX516 in Alzheimer's Disease
Glutamate is an amino acid released by brain cells that acts to excite other cells. Glutamate attaches to special sites on cells called AMPA (alpha-amino-2,3-dihydro-5 methyl 3-oxo-4-isoxazolepropanoic acid) receptors. The brain cells responsible for releasing glutamate are damaged in Alzheimer's disease and other conditions affecting thinking and reasoning.
Researchers would like to see if giving patients a drug that attaches to AMPA receptors improves the symptoms of Alzheimer's disease.
Read more
CX516 (Ampalex) is a test drug that affects the AMPA receptors. This study will investigate the effectiveness and safety of CX516 on patients with Alzheimer's disease.
Patients will be given capsules of CX516 or placebo (sugar pill that neither harms nor helps) for up to 16 weeks in different amounts. The effectiveness of the drug will be measured by neurological tests. Safety will be monitored by frequent check-ups and lab examinations.
Read the detailed description
Stimulation of neuronal excitatory amino acid receptors is an important step in the formation of memory. It is unknown whether stimulation of these receptors in patients with Alzheimer's disease and dementing disorders will improve cognitive function. To determine whether positive modulation of AMPA receptors, active in animal models of dementia, can improve cognitive function in demented patients, CX516, at a dose of 900mg TID, will be administered orally for 12 weeks in patients with dementia. In this randomized, controlled proof-of-principle study, drug-induced alterations in intellectual function will be measured by standardized neuropsychological tests. Safety will be monitored by frequent clinical assessments and laboratory tests.
- Conditions
- Alzheimer's Disease, Dementia
- Being tested
- CX516 (Ampalex)
- Keywords
- Dementia, Glutamate, Clinical Trial, Neurotransmitter, Alzheimer's Disease
- Medical subject headings
- Alzheimer Disease, Dementia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CX516 (Ampalex)Drug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 1999 (estimated)
- Study startDec 1996
- Study completionNov 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Alzheimer's DiseaseStudies of the same condition, open and under way.
- More trials run by National Institute of Neurological Disorders and Stroke (NINDS)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Enrolment
- 40 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00001662
- Sponsor's protocol ID
- 970049
- Other IDs
- 97-N-0049
- Status last verified
- Nov 2005
- First submitted
- 3 Nov 1999
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Arai A, Kessler M, Rogers G, Lynch G. Effects of a memory-enhancing drug on DL-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor currents and synaptic transmission in hippocampus. J Pharmacol Exp Ther. 1996 Aug;278(2):627-38.
PubMed 8768713Granger R, Staubli U, Davis M, Perez Y, Nilsson L, Rogers GA, Lynch G. A drug that facilitates glutamatergic transmission reduces exploratory activity and improves performance in a learning-dependent task. Synapse. 1993 Dec;15(4):326-9. doi: 10.1002/syn.890150409.
PubMed 8153879Greenamyre JT, Maragos WF, Albin RL, Penney JB, Young AB. Glutamate transmission and toxicity in Alzheimer's disease. Prog Neuropsychopharmacol Biol Psychiatry. 1988;12(4):421-30. doi: 10.1016/0278-5846(88)90102-9.
PubMed 2900537
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tolerability and Primary Efficacy of CX516 in Alzheimer's Disease
- ClinicalTrials.gov ID
- NCT00001662
- Acronym / sponsor ID
- 970049
- Conditions
- Alzheimer's Disease, Dementia
- Keywords
- Dementia, Glutamate, Clinical Trial, Neurotransmitter, Alzheimer's Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- Dec 1996
- Study completion
- Nov 2005
- First posted
- 4 Nov 1999 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Glutamate is an amino acid released by brain cells that acts to excite other cells. Glutamate attaches to special sites on cells called AMPA (alpha-amino-2,3-dihydro-5 methyl 3-oxo-4-isoxazolepropanoic acid) receptors. The brain cells responsible for releasing glutamate are damaged in Alzheimer's disease and other conditions affecting thinking and reasoning.
Researchers would like to see if giving patients a drug that attaches to AMPA receptors improves the symptoms of Alzheimer's disease.
CX516 (Ampalex) is a test drug that affects the AMPA receptors. This study will investigate the effectiveness and safety of CX516 on patients with Alzheimer's disease.
Patients will be given capsules of CX516 or placebo (sugar pill that neither harms nor helps) for up to 16 weeks in different amounts. The effectiveness of the drug will be measured by neurological tests. Safety will be monitored by frequent check-ups and lab examinations.
Detailed description
Stimulation of neuronal excitatory amino acid receptors is an important step in the formation of memory. It is unknown whether stimulation of these receptors in patients with Alzheimer's disease and dementing disorders will improve cognitive function. To determine whether positive modulation of AMPA receptors, active in animal models of dementia, can improve cognitive function in demented patients, CX516, at a dose of 900mg TID, will be administered orally for 12 weeks in patients with dementia. In this randomized, controlled proof-of-principle study, drug-induced alterations in intellectual function will be measured by standardized neuropsychological tests. Safety will be monitored by frequent clinical assessments and laboratory tests.
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (16 listed)
- Study subjects will satisfy NINCDS-ADRDA criteria for probable Alzheimer's disease.
- Dementia severity will be mild to moderate range with Mini-Mental Status Examination total score between 12 and 26, inclusive.
- The modified Hachinski Ischemia Score must be less than 4, and brain MRI performed within 15 months of enrollment must be compatible with the diagnosis of Alzheimer's disease.
- Dementia must be present historically for at least one year. Baseline electroencephalogram must not show significant epileptiform features.
- Study subjects will show deficits in at least two cognitive spheres, including memory.
Key exclusion criteria (8 listed)
- Hemispheric stroke, hydrocephalus, subdural hematoma, or mass lesion on neuroimaging study; "epileptiform" baseline EEG or known seizure disorder; head trauma with loss of consciousness concurrent with onset of dementia; chronic CNS infection (positive MHA-TP or FTA-ABS acceptable if luetic brain disease excluded by documented studies or treatment).
- Acute serious infection, including hepatitis; hypothyroidism (TSH greater than 6.0 microunits/mL); folic acid deficiency (less than 0.9 ng/mL); vitamin B12 deficiency (less than 160 pg/mL) within one year prior to enrollment; severe renal insufficiency (creatinine clearance less than 25 mL/min, BUN greater than 40 mg/dL, or serum creatinine greater than 2.0 mg/dL); hepatic insufficiency (SGPT or SGOT greater than 3 x upper limit of normal, or total bilirubin greater than 2.0 mg/dL). Due to the serious adverse event transient agranulocytosis report in another study of CX516, patients will neutropenia or low normal white blood cell counts (greater than or equal to 3.5 K/microliter) will be excluded from this study.
- Depression if present during screening. Depression will be diagnosed clinically and with depression rating scale(s), such as Hamilton Depression Rating Scale, if needed.
- Administration of tacrine, donepezil, rivastigmine, galantamine, anti-depressants are prohibited within thirty days prior to enrollment.
- Any hepatic, cardiovascular, gastrointestinal, or hematological illness which could interfere with drug absorption, distribution, metabolism, or excretion; known hypersensitivity to CX516 or its vehicle; inability to swallow tablets or to comply with medication schedule; no significant care giver; uncorrectable loss of hearing or eyesight that precludes psychometric testing; inability to comprehend instructions or to respond to test items.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CX516 (Ampalex) | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2008.
- Background: PubMed 8768713Arai A, Kessler M, Rogers G, Lynch G. Effects of a memory-enhancing drug on DL-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor currents and synaptic transmission in hippocampus. J Pharmacol Exp Ther. 1996 Aug;278(2):627-38.
- Background: PubMed 8153879Granger R, Staubli U, Davis M, Perez Y, Nilsson L, Rogers GA, Lynch G. A drug that facilitates glutamatergic transmission reduces exploratory activity and improves performance in a learning-dependent task. Synapse. 1993 Dec;15(4):326-9. doi: 10.1002/syn.890150409.
- Background: PubMed 2900537Greenamyre JT, Maragos WF, Albin RL, Penney JB, Young AB. Glutamate transmission and toxicity in Alzheimer's disease. Prog Neuropsychopharmacol Biol Psychiatry. 1988;12(4):421-30. doi: 10.1016/0278-5846(88)90102-9.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing CX516 (Ampalex) in people with Alzheimer's Disease and Dementia, run by National Institute of Neurological Disorders and Stroke (NINDS) 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 16 inclusion and 8 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 4 Mar 2008. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00001662, which also lists 3 linked publications.
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 4 Mar 2008.