Name: HF0220
Therapy Type: Small Molecule (timeline)
Target Type: Inflammation (timeline)
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Discontinued)
Company: Newron
Last Updated: 10 Aug 2013
No Available Further Reading
Name: GSK239512
Therapy Type: Small Molecule (timeline)
Target Type: Cholinergic System (timeline), Other Neurotransmitters (timeline)
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Discontinued)
Company: GlaxoSmithKline (GSK)
GSK was developing this histamine H3 receptor antagonist for the treatment of Alzheimer's, schizophrenia, and multiple sclerosis. The rationale was to boost release in the brain of histamine, acetylcholine, noradrenaline, and dopamine in an attempt to enhance cognitive processes. In particular, histamine H3 receptor antagonism has been proposed to increase cholinergic signaling, which wanes with neurodegeneration in AD (Passani and Blandina, 1998; Bembenek et al., 2008; Bitner et al., 2011; Brioni et al., 2011). Blocking this receptor has been a target of several small-molecule therapeutic programs for cognition disorders at other companies as well, e.g. ABT-288, S38093.
Between 2007 and 2014, GSK conducted six clinical trials on this compound, three in Alzheimer's, two in multiple sclerosis, and one in schizophrenia.
Phase 1 studies assessed safety, pharmacokinetics, maximum tolerated dose, and brain distribution with the help of a PET imaging probe to this drug. A dose titration regimen emerging from some of these studies is published in the peer-reviewed literature (Nathan et al., 2013).
Also published are data from a Phase 2 study, in which 196 people with mild to moderate Alzheimer's disease were treated with GSK239512 or placebo for four months. The antagonist improved episodic memory but not other cognitive domains or clinical measures. It caused mild to moderate adverse events, predominantly headaches, dizziness, and problems sleeping (Grove et al., 2014). As of November 2015, this compound was no longer listed in GSK’s development pipeline.
For all clinical trials of GSK239512, see clinicaltrials.gov.
Last Updated: 15 Jan 2016
No Available Comments
No Available Further Reading
Name: ABT-288
Therapy Type: Small Molecule (timeline)
Target Type: Cholinergic System (timeline), Other Neurotransmitters (timeline)
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Discontinued)
Company: AbbVie
Abbott, now AbbVie, was developing this histamine H3 receptor antagonist for the treatment of cognitive deficits in Alzheimer's and schizophrenia. The rationale was to boost release in the brain of histamine, acetylcholine, noradrenaline, and dopamine in an attempt to enhance cognitive processes. In particular, the approach has been proposed to increase cholinergic signaling, which wanes with neurodegeneration in AD (Passani and Blandina, 1998; Bembenek et al., 2008; Bitner et al., 2011, Brioni et al., 2011). Blocking the receptor has been a target of several small-molecule therapeutic programs for cognition disorders at other companies as well, e.g. GSK239512, S 38093.
Three clinical trials are registered on this compound. A single- and multiple-ascending dose study in healthy volunteers was reported to have been generally safe and well-tolerated, with the most frequent side effects being related to sleep, nausea, and dizziness. The 1 and 3 mg per day doses were subsequently evaluated in Phase 2 (Othman et al., 2012).
A subsequent Phase 2 trial of adjunct treatment with ABT-288 in 242 people with mild to moderate Alzheimer's disease who were on stable donepezil treatment ended early. It met futility criteria when the ADAS-cog outcome was statistically significantly improved on donepezil but not on ABT-288 (Haig et al., 2014). A third Phase 2 trial was conducted in schizophrenia. ABT-288 development appears to have been discontinued.
For details on clinical studies, see clinical trials.gov.
Last Updated: 15 Jan 2016
No Available Comments
No Available Further Reading
Name: Lornoxicam
Therapy Type: Small Molecule (timeline)
Target Type: Inflammation (timeline)
Condition(s): Alzheimer's Disease, Mild Cognitive Impairment
U.S. FDA Status: Alzheimer's Disease (Discontinued), Mild Cognitive Impairment (Discontinued)
Company: JSW Lifesciences
Approved for: Pain in US
Last Updated: 10 Aug 2013
No Available Comments
No Available Further Reading
Name: Acitretin
Synonyms: Soriatane , Neotigason, RO 101670
Therapy Type: Small Molecule (timeline)
Target Type: Amyloid-Related (timeline)
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Phase 2)
Company: Actavis, Allergan plc
Approved for: Psoriasis in US
Acitretin is a retinoid drug used primarily to treat severe psoriasis. It can cause birth defects and other side effects typical of vitamin A overdose, including hair loss, elevated triglyceride levels, and drying of mucosal membranes, and therefore is used only in patients who do not respond to less-toxic psoriasis drugs. Acitretin acts as a retinoic acid receptor agonist. In preclinical models it increases expression of ADAM-10, the physiological α-secretase of the human amyloid precursor protein (APP). Acitretin was reported to boost non-amyloidogenic processing of APP in neuroblastoma cells and reduce Aβ levels in APP/PS-1 transgenic mice (see Tippman et al., 2009). It reportedly crosses the blood-brain barrier in mice (Holthoewer et al., 2012).
In 2010, a Phase 2 trial began at two sites, in Mainz and Rostock, Germany. It aimed to investigate efficacy and tolerability of a four-week course of 30 mg/day of acitretin capsules in 76 men and women with mild to moderate Alzheimer's disease. The primary outcome was differences in CSF APPSα levels, as measured at four weeks (see European Clinical Trials Database Trial Register). The trial ended in 2013 and was published in 2014. Twenty-one patients were randomized to acitretin (11) or placebo (10); none dropped out. The investigators reported a 25 percent intra-individual increase in CSF-APPsα in the treatment group between baseline and one month on aitrcetin, with statistical significance of 0.05 when controlled for older ages in the placebo than treatment group. APPs-β was reported to trend lower but was not statistically significant. CSF Aβ42, phospho-tau, and total tau remained unchanged. Side effects were as expected, with dryness of skin and mucous membranes, skin scaling, and hair loss. According to the authors, this pilot study provides proof of mechanism of increased ADAM-10 activity in response to acitretin in AD (Endres et al., 2014).
| Sponsor | Clinical Trial | 2008 | 2009 | 2010 | 2011 | 2012 | 2013 | 2014 | 2015 | 2016 | 2017 | 2018 | 2019 | 2020 | 2021 | 2022 | 2023 | 2024 | 2025 | 2026 | 2027 | 2028 | 2029 | 2030 | 2031 | 2032 | 2033 | 2034 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT01078168 |
N=76
|
Last Updated: 09 Oct 2015
No Available Comments
No Available Further Reading
Name: ABT-384
Therapy Type: Small Molecule (timeline)
Target Type: Other (timeline)
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Discontinued)
Company: AbbVie
This is a selective 11-β-hydroxysteroid dehydrogenase type 1 (HSD-1) inhibitor that was evaluated to test the hypothesis that elevated cortisol levels in the brain contribute to cognitive impairment.
In 2009 and 2010, Abbvie conducted two phase 1 studies to evaluate safety, pharmacokinetics and -dynamics in healthy and elderly participants (Liu et al., 2013; Katz et al., 2013).
Between May 2010 and July 2011, Abbvie ran a multicenter Phase 2 trial. Conducted at 30 sites in four different countries, it compared 10 and 50 mg of ABT-384 or placebo, given once-daily for three months, in people with mild to moderate Alzheimer's disease for change from baseline on the ADAScog13. After randomizing 267 participants, the study was stopped for futility. Neither dose of ABT-384 affected cognitive performance; whereas the active comparator donepezil did (Marek et al., 2014). No further development was reported.
Last Updated: 29 Nov 2019
No Available Comments
No Available Further Reading
Name: Intepirdine
Synonyms: RVT-101, SB 742457 , GSK 742457
Therapy Type: Small Molecule (timeline)
Target Type: Other Neurotransmitters (timeline)
Condition(s): Alzheimer's Disease, Dementia with Lewy Bodies
U.S. FDA Status: Alzheimer's Disease (Discontinued), Dementia with Lewy Bodies (Discontinued)
Company: Axovant Sciences Ltd.
Originally developed by GSK under the name SB-742457, RVT-101/intepirdine is an antagonist of the serotonin receptor 6 (5-HT)6, a largely CNS-specific member of the serotonin receptor subfamily. The serotonergic neurotransmitter system is impaired as Alzheimer’s develops and progresses, and modulating it is seen as a potential therapeutic avenue (Upton et al., 2008). SB-742457 has been reported to reverse both experimentally induced and age-related learning deficits in rats (de Bruin et al., 2013; Callaghan et al., 2012). This drug does not target central AD pathways of Aβ amyloidosis and tauopathy; rather, it represents an approach to enhancing cognition in Alzheimer's and other forms of dementia (Codony et al., 2011).
Several Phase 1 studies compared SB-742457 in capsule and tablet formulations, and showed that the compound was well-tolerated.
GSK completed four Phase 2 studies of this compound, all in patients with mild to moderate AD. Between 2005 and 2007, a six-month dose-ranging trial of SB-742457 monotherapy measured the effect that 5 mg, 15 mg, or 35 mg of the drug taken once daily had on cognition (ADAS-cog) and global clinical function (Change plus Caregiver Input, CIBIC-plus) in 371 patients in the European Union, Croatia, Russia, South Africa, Chile, South Korea, and New Zealand. That trial reported a small but dose-dependent benefit of the study drug on both measures, as well as acceptable tolerability (Maher-Edwards et al., 2011; August 2008 conference news). Other Phase 2 trials failed to meet their primary endpoints, but suggested some benefit of intepirdine as an adjunct to donepezil (Mayer-Edwards et al., 2011; Mayer-Edwards et al., 2015).
In December 2014, Axovant Sciences acquired rights to this drug and renamed it RVT-101, and then intepirdine. At AAIC 2015, Axovant presented a more complete analysis of prior Phase 2b GSK data on RVT-101 added to donepezil that had been analyzed previously based on the intent-to-treat population, and came up with a slightly larger effect size on essentially similar efficacy results. A Phase 3 program for mild to moderate AD, as well as trials in other forms of dementia, was in planning.
In 2015, Axovant began MINDSET, a registration trial of a six-month course of 35 mg RVT-101 once daily added to stable donepezil therapy in 1,315 patients with mild to moderate AD. In December 2015, Axovant presented a poster at the CTAD conference claiming nearly full receptor occupancy at the dose used in Phase 3, and announced plans to evaluate this drug in dementia with Lewy bodies (DLB). Set to run until October 2017, MINDSET aimed to confirm the prior GSK study, with a standard co-primary outcome of ADAS-Cog and ADCS-ADL. In September 2017, Axovant released topline results stating the drug had failed to improve cognition or activities of daily living relative to placebo (Sept 2017 news). The 12-month open-label extension study of MINDSET continued until negative results for the DLB trial of intepirdine were reported several months later. Trial results were published after peer review (Lang et al., 2021).
In January 2016, HEADWAY-DLB, a Phase 2 study, started enrolling an anticipated 240 patients with DLB to compare a six-month course of 35 or 70 mg intepirdine to placebo for change since baseline on the CIBIC+ scale. Secondary endpoints included visual hallucinations and safety parameters. This trial was set to run until March 2018 at 39 locations in the United States and Europe, and offered a six-month extension for completers. In October 2016, Axovant started a trial in 40 people with either AD, DLB, or Parkinson's disease dementia (PDD) to evaluate a three-month course of 35 mg of intepirdine or placebo for effects on quantitative gait measurement. This study was to run for one year at two U.S. sites. However, in January 2018, Axovant reported negative results from both the Headway-DLB and PDD gait trials, announcing an end to extension dosing in MINDSET and HEADWAY-DLB, and discontinuation of intepirdine development (Jan 2018 news).
For trials of this compound, see clinical trials.gov.
| Sponsor | Clinical Trial | 2013 | 2014 | 2015 | 2016 | 2017 | 2018 | 2019 | 2020 | 2021 | 2022 | 2023 | 2024 | 2025 | 2026 | 2027 | 2028 | 2029 | 2030 | 2031 | 2032 | 2033 | 2034 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Axovant Sciences Ltd. | NCT02585934 |
N=1315
|
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| Axovant Sciences Ltd. | NCT02669433 |
N=484RESULTS
|
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| Axovant Sciences Ltd. | NCT02586909 |
N=1099RESULTS
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| Axovant Sciences Ltd. | NCT02910102 |
N=38RESULTS
|
Last Updated: 25 Jun 2021
No Available Comments
No Available Further Reading
Name: Ketasyn
Synonyms: Axona, Caprylic Acid, AC-1202
Therapy Type: Supplement, Dietary (timeline)
Target Type: Other (timeline)
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Phase 4)
Status in Select Countries: Sold in the United States as a medical food.
Company: Cerecin Pte. Ltd.
This is a nutritional beverage. Ketasyn/AC-1202 was tested in Phase 1 and 2 safety/dosing trials, but in Phase 2 missed its primary endpoint and was not advanced to Phase 3 efficacy trials. Rather, in 2009 its developer, Accera Inc., since renamed Cerecin, brought it to market as a once-daily medical food called Axona. Medical foods do not undergo pre-market FDA review or approval. Unlike dietary supplements, they are not available over the counter but are prescribed by physicians.
Axona is a proprietary formulation of processed coconut or other oils and glycerin. Its active ingredient is caprylic acid, along with other medium-chain triglycerides. Caprylic acid metabolism in the liver leads to substances called "ketone bodies," which cross the blood-brain barrier. These have been hypothesized to provide an alternative to glucose as the brain's source of energy in conditions marked by impaired neuronal metabolism, such as Alzheimer's. Brain imaging by FDT-PET shows cerebral glucose hypometabolism in regions affected by Alzheimer's.
Axona's effectiveness has been called into question by experts in the field, e.g. , Oct 2009 news series. As a result of media stories covering the controversy (e.g., ABC News), demand for coconut oil as a cheaper source of caprylic acid rose. However, there is no scientific evidence that it is effective.
On 26 December 2013, the FDA issued a warning letter charging Accera with 'false and misleading labeling.' Ketasyn, the FDA elaborated, does not meet the statutory definition of a medical food, but is instead an unapproved drug (see FDA 2013 Warning Letters). In May 2014, Accera was subject to a related class action lawsuit before the 11th Judicial Circuit court in Florida (see Law360 story).
The company is testing other formulations of caprylic acid triglyceride for possible FDA approval (see Tricaprilin).
In October 2018, Accera re-branded itself as Cerecin, following investments from a Singapore-based agribusiness group and a private equity fund backed by Nestlé (press release). The company plans to market Axona in Asia-Pacific countries.
A two-week open-label safety, tolerability, and pharmacokinetics study of different formulations of Ketasyn in 60 healthy elderly volunteers preceded two Phase 2 studies.
From 2004 to 2006, a 90-day, double-blind, multicenter trial in 152 patients with mild to moderate Alzheimer's disease evaluated Ketasyn against the Alzheimer's Disease Assessment Scale—cognitive subscale (ADAS-cog), the Alzheimer's Disease Cooperative Study—Clinician's Global Impression of Change (ADCS-CGIC), and the Mini-Mental State Exam (MMSE). This trial was reported to have improved cognitive function in participants on Ketasyn at the 45-day trial mid-point, though the difference was no longer statistically significant by 90 days. In ApoE4 non-carriers, the effect did remain statistically significant by 90 days. Adverse event discontinuations were 23 percent, mostly for diarrhea, flatulence, and dyspepsia (Henderson et al., 2009).
From 2006 to 2007, a second 90-day trial in 150 older adults with "normal" loss of memory abilities since early adult life evaluated Ketasyn. This trial used changes in the Psychologix and Cogscreen Test Batteries, RAVLT (Rey Auditory Verbal Learning Test), as primary outcome. The results were not published.
In 2010, Accera started a PET study at the University of California, Los Angeles, to evaluate the effects of Axona on cerebral metabolism in 22 participants with Alzheimer's disease. This trial measures regional cerebral blood flow in response to 45 days treatment with Ketasyn, comparing ApoE4 carriers to non-carriers. According to published results, participants lacking an E4 allele showed an increase in regional blood flow in parts of the cortex and the cerebellum and hypothalamus, while ApoE4 carriers did not (Torosyan et al., 2018).
For all clinical trials on Ketasyn, see clinicaltrials.gov.
Last Updated: 03 Feb 2021
No Available Comments
No Available Further Reading
Name: G-CSF
Synonyms: Filgrastim
Therapy Type: Small Molecule (timeline)
Target Type: Other (timeline)
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Phase 2)
Approved for: Neutropenia in US
Last Updated: 10 Aug 2013
No Available Comments
No Available Further Reading
Name: Levetiracetam
Synonyms: Keppra
Chemical Name: (S)-α-Ethyl-2-oxo-1-pyrrolidineacetamide
Therapy Type: Small Molecule (timeline)
Target Type: Amyloid-Related (timeline), Other (timeline)
Condition(s): Alzheimer's Disease, Parkinson's Disease
U.S. FDA Status: Alzheimer's Disease (Phase 2), Parkinson's Disease (Discontinued)
Company: UCB S.A.
Approved for: Epilepsy and Partial Seizures in U.S., European Union, plus about 20 other countries
Levetiracetam is an atypical anti-convulsant medication and a modulator of the synaptic vesicle protein modulator SV2A. It was developed for the treatment of epilepsy but, as a pyrrolidone acetamide, is chemically unrelated to most other anti-convulsives. Levetiracetam is available as an oral syrup, an intravenous infusion, and immediate- and extended-release tablets. Generic equivalents of these formulations are on the market as well, and the drug is widely used. Its side effects include sleepiness, headache, lack of energy, and others.
This compound's mechanism of action is not fully understood. It does not act on the GABAergic system and is inactive at classic receptor sites linked to epileptic seizures, such as amino-acid-related receptors, adenosine receptors, and ion channels (Sills et al., 1997). Early on, inhibition of calcium signaling or depolarizing currents were proposed as possible mechanisms of action (Margineanu and Wülfert, 1997).
In recent years, Alzheimer’s research has characterized Aβ-induced hyperactivation, aberrant network activity, and nonconvulsive seizure phenotypes in the J20, APP23, APP/PS1, and in certain strains of Tg2576 transgenic mouse models of AD amyloidosis (Sep 2007 news; Lalonde et al., 2005; Minkeviciene et al., 2009; Shi et al., 2013). In J20 mice, levetiracetam was reported to quiet epileptiform activity in circuits of the medial temporal lobe network, as well as reverse hyperactivity in behavioral assays and deficits in spatial learning assays (Aug 2012 news). Low doses of the drug reportedly reduce hippocampal hyperactivation and improved memory performance in an aging rat model (Koh et al., 2010). In APP knock-in mice, chronic administration of levetiracetam was reported to reduce levels of Aβ42, the β-carboxyl-terminal fragment bur not full-length APP, reduce plaque burden, and to restore levels of presymptomatic endocytic proteins (Rao and Savas, 2021).
In humans, observational research has linked hippocampal hyperactivity and nonconvulsive seizures to cognitive decline in the early stages of Alzheimer's disease, such as amnestic mild cognitive impairment (aMCI, Dec 2011 news; July 2013 news; Vossel et al., 2016). Further studies reported that seizures or subclinical epileptiform brain activity in people with AD coincide with faster loss of cognitive capabilities and more severe disease (Horvath et al., 2021; Voglein et al., 2020).
A proprietary, low-dose formulation of levetiracetam, AGB101, is in a Phase 3 trial evaluating its ability to improve cognition and slow disease progression in people with MCI and AD.
A one-year study of levetiracetam at 500-2,000 mg daily in Alzheimer's patients who had seizures reported improved attention, verbal fluency, and good tolerability for its use in controlling seizures in AD (Cumbo and Ligori, 2010). It is unclear whether these benefits derived from reduced seizures or global cognitive benefits.
Levetiracetam doses of 1,000 mg/day are routinely used in older people with epilepsy. Several studies have examined lower doses to see if they can normalize brain activity and improve cognition in people with mild cognitive impairment or AD. In one single-center, placebo-controlled Phase 2 trial of low-dose levetiracetam, 17 people with aMCI and 17 age-matched controls who received a two-week course of 250 mg daily reportedly reduced hippocampal activity as measured by fMRI and improved performance on a hippocampal memory task. Other tests in a neuropsychological test battery showed no response (May 2012 news).
In 2010–2012, researchers at Johns Hopkins University Medical School conducted a within-subject crossover, dose-finding Phase 2 study of low-dose levetiracetam in people with amnestic mild cognitive impairment (aMCI) and a clinical dementia rating (CDR) of 0.5 at screening; controls had a CDR of zero. The trial compared 125, 250, and 500 mg of levetiracetam per day against placebo for their effect on neuronal activity in the hippocampus and entorhinal cortex, as well as for performance on a memory task performed while in an MRI scanner. The study enrolled 69 aMCI patients and 24 controls, and analyzed data from 54 patients and 17 controls; 15 participants dropped out; seven moved while inside the scanner. At the two lower doses, levetiracetam was reported to have improved performance on the scanning memory task; the highest dose yielded no further improvement. The low doses were also reported to have reduced abnormal hyperactivity in the hippocampal dentate gyrus and CA3 regions, and to have boosted abnormal hypoactivation in the entorhinal cortex, both measured by fMRI. Full results were published in a peer-reviewed journal (for paper and commentary, see Bakker et al., 2015).
A 2012–2013 study at Beth Israel Deaconess Medical Center, Boston, compared single administration of 2.5 mg/kg and 7.5 mg/kg of levetiracetam to placebo. This trial enrolled 12 patients with mild AD and seizures, and used perfusion MRI to evaluate whether levetiracetam normalized blood flow in the course of controlling seizures. Memory and executive function tests were secondary outcomes. A paper on this study did not report on blood flow; it did report that the higher dose had network effects, specifically changes in coherence of the delta, low-beta, and high-beta bands. Cognition was unchanged (Musaeus et al., 2017).
In June 2014, a Phase 2a study at the University of California, San Francisco, and the University of Minnesota, Twin Cities, began enrolling 34 people with AD. This 12-week cross-over trial evaluated 125 mg twice-daily levetiracetam for its ability to improve executive function as per the NIH-EXAMINER composite score, reduce the frequency of epileptiform activity, and improve cognitive function and performance on a virtual navigation task. The trial was originally intended only for people with evidence of seizure activity, but that requirement was later dropped to speed recruitment. The study was completed in July 2020, and results are published (Vossel et al., 2021). Levetiracetam treatment did not change the primary outcome, or any secondary measures in the group as a whole. In a subgroup analysis that compared nine participants with epileptiform brain activity to 13 without, the drug improved performance on two secondary outcomes related to executive function and the navigational task in those with clinical or subclinical seizures. Adverse events were mild; no one left the study because of side effects.
An additional Phase 2 study at Beth Israel Deaconess Medical Center began in August 2019, to determine whether levetiracetam normalizes cortical hyperexcitability, brain network function abnormalities, and cognitive dysfunction in 85 people with early AD. Participants must be between 50 and 80 years old, with a positive PET or CSF markers for brain amyloid, and a Clinical Dementia Rating of 0.5–1.0. In a crossover design, patients receive placebo, 250 mg, or 1000 mg levetiracetam daily for four weeks, with a four-week washout between. Primary outcome measures include change in neuropsychological test battery, plus EEG and other measures of cortical excitability and functional connectivity. Healthy controls with CDR=0 will also be evaluated, but receive no treatment. The trial will end in November 2023.
In October 2018, a Phase 2 study at the University of Oxford began enrolling 30 participants with mild to moderate AD and no history of previous seizures to receive levetiracetam 1,000 mg per day for four weeks. Primary outcome is change in accuracy on a computer-based hippocampal-dependent memory test; secondary outcomes include safety, mood, quality of life. Participants will get an EEG before the study to look for patterns that predict who will benefit from the treatment. The protocol for this study, named ILiAD, is published (Sen et al., 2021).
Starting in January 2020, a Phase 2 trial at Walter Reed National Military Medical Center, Bethesda, Maryland, will enroll 65 participants with clinical AD and neuropsychiatric symptoms. Those with detectable epileptiform activity on EEG will receive 500 mg levetiracetam twice a day for one year. The primary outcome is change on the neuropsychiatric inventory; secondary outcomes include change in measures of AD severity, quality of life, and cognitive ability.
Levetiracetam has also been tested in patients with Parkinson's disease. Prompted by preclinical data suggesting that levetiracetam reduces side effects of long-term levodopa therapy in nonhuman primates (Bezard et al., 2004), numerous small clinical trials were conducted in patients with Parkinson's and levodopa-induced dyskinesia. One pilot trial reported longer “on” time without dyskinesia and shorter “off” time with dyskinesia, but subsequent randomized controlled trials produced mixed results. Some studies indicated modest improvement, others did not, and yet others cautioned that PD patients poorly tolerated levetiracetam (see Wolz et al., 2010; Stathis et al., 2011; Wong et al., 2011; Lyons and Pahwa, 2006).
For clinical trials on levetiracetam in MCI/AD, see clinicialtrials.gov.
| Sponsor | Clinical Trial | 2007 | 2008 | 2009 | 2010 | 2011 | 2012 | 2013 | 2014 | 2015 | 2016 | 2017 | 2018 | 2019 | 2020 | 2021 | 2022 | 2023 | 2024 | 2025 | 2026 | 2027 | 2028 | 2029 | 2030 | 2031 | 2032 | 2033 | 2034 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT01044758 |
N=144
|
Last Updated: 06 Oct 2021
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