DAOIBplusAO Phase 2 (NCT06467539): Novel NMDA-Enhancing Agent with Antioxidant Augmentation
Overview
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DAOIBplusAO is a novel combination therapy being investigated in this Phase 2 trial at Chang Gung Memorial Hospital in Kaohsiung City, Taiwan. The trial evaluates whether combined treatment with an NMDA-enhancing agent (DAOIB) and an antioxidant (AO) provides better cognitive outcomes than DAOIB alone in patients with early-phase dementia["@clinicaltrialsgov"].
...DAOIBplusAO Phase 2 (NCT06467539): Novel NMDA-Enhancing Agent with Antioxidant Augmentation
Overview
Mermaid diagram (expand to render)
DAOIBplusAO is a novel combination therapy being investigated in this Phase 2 trial at Chang Gung Memorial Hospital in Kaohsiung City, Taiwan. The trial evaluates whether combined treatment with an NMDA-enhancing agent (DAOIB) and an antioxidant (AO) provides better cognitive outcomes than DAOIB alone in patients with early-phase dementia["@clinicaltrialsgov"].
Previous studies have found that NMDA-enhancing agents can improve cognitive function in patients with early-phase dementia["@nmdaDementia2006"]. Additionally, several drugs with antioxidant properties have been tested in clinical trials for dementia treatment["@antioxidantAD2005"]. This trial tests the hypothesis that combined treatment may be superior to monotherapy.
| Attribute | Details |
|-----------|---------|
| NCT Number | NCT06467539 |
| Sponsor | Chang Gung Memorial Hospital |
| Drug | DAOIB plus Antioxidant (AO) |
| Phase | Phase 2 |
| Indication | Alzheimer's Disease, Mild Cognitive Impairment |
| Status | Recruiting |
| Participants | 80 |
| Study Start | 2024-06-19 |
| Estimated Completion | 2027-05 |
| Location | Kaohsiung City, Taiwan |
| Duration | 24 weeks |
Mechanism of Action
NMDA Enhancement
The NMDA (N-methyl-D-aspartate) receptor is a glutamate receptor subtype critical for synaptic plasticity and memory formation. In Alzheimer's disease:
- Glutamate signaling is dysregulated
- NMDA receptor function may be impaired
- This contributes to synaptic dysfunction and cognitive decline
NMDA-enhancing agents modulate NMDA receptor activity to improve synaptic signaling and potentially preserve cognitive function.
Antioxidant Augmentation
Oxidative stress plays a key role in Alzheimer's disease pathogenesis:
- Amyloid-beta and tau pathology increase reactive oxygen species (ROS)
- Mitochondrial dysfunction generates excess ROS
- Antioxidant defenses diminish with age
Antioxidant compounds may:
- Reduce oxidative damage to neurons
- Protect synaptic function
- Decrease neuroinflammation
Rationale for Combination Therapy
The combination approach addresses multiple pathogenic pathways simultaneously:
| Component | Target | Purpose |
|-----------|--------|---------|
| DAOIB | NMDA receptors | Enhance synaptic signaling |
| AO | Oxidative stress | Reduce ROS damage |
This dual mechanism may provide additive or synergistic benefits compared to either approach alone.
Eligibility Criteria
Inclusion Criteria
- Clinical diagnosis of Alzheimer's disease or mild cognitive impairment
- MMSE score between 10-26
- CDR score of 1 or 0.5
Exclusion Criteria
- Hachinski Ischemic Score > 4
- Substance abuse/dependence
- Parkinson disease, epilepsy, or dementia with psychotic features
- Major depressive disorder
- Major physical illnesses
- Severe visual or hearing impairment
Demographics
- Age range: 50-90 years
- Sex: All
Trial Design
Study Type
- Interventional
- Allocation: Randomized
- Intervention Model: Parallel
- Primary Purpose: Treatment
- Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Arms
| Arm | Type | Intervention |
|-----|------|--------------|
| Experimental | Drug | DAOIB plus Antioxidant agent (AO) |
| Comparator | Placebo | DAOIB plus Placebo |
Treatment Duration
- 24 weeks (oral administration)
Outcome Measures
Primary Outcomes
| Measure | Description | Time Frame |
|---------|-------------|------------|
| ADAS-Cog Change | Alzheimer's Disease Assessment Scale - Cognitive subscale change from baseline | Week 0, 8, 16, 24 |
The ADAS-Cog consists of 11 tasks assessing cognitive function, with scores ranging from 0 (best) to 70 (worst).
Secondary Outcomes
| Measure | Description | Time Frame |
|---------|-------------|------------|
| CIBIC+ | Clinician's Interview-Based Impression of Change plus Caregiver Input | Week 8, 16, 24 |
| MMSE | Mini-Mental Status Examination score change | Week 8, 16, 24 |
| CDR-SB | Clinical Dementia Rating Scale Sum of Boxes | Week 8, 16, 24 |
| ADCS-MCI-ADL | Alzheimer's Disease Cooperative Study scale for ADL in MCI | Week 8, 16, 24 |
| SF-36 | Medical Outcomes Study Short-Form-36 (quality of life) | Week 8, 16, 24 |
| Composite Cognitive Tests | Battery including speed of processing, working memory, learning and memory | Week 0, 24 |
Clinical Significance
Rationale for Early Intervention
This trial targets early-phase dementia for several reasons:
Greater reserve capacity for cognitive improvement
Less irreversible neurodegeneration
Greater treatment responsiveness
Opportunity to slow disease progressionImportance of Combination Therapy
Monotherapy approaches have shown limited efficacy in AD:
- Single mechanism targeting may be insufficient
- Multiple pathogenic pathways require multi-target approaches
- Combination therapy is standard in other chronic diseases
Cross-Links to NeuroWiki
- [Alzheimer's Disease](/diseases/alzheimers-disease) — Target indication
- [Mild Cognitive Impairment](/conditions/mild-cognitive-impairment) — Related condition
- [NMDA Receptors](/entities/nmda-receptors) — Drug target mechanism
- [Oxidative Stress](/mechanisms/oxidative-stress) — Secondary mechanism
- [Antioxidants in AD](/therapeutics/antioxidants-alzheimers) — Related therapeutic approach
- [Taiwan](/countries/taiwan) — Trial location
References
Unknown, ClinicalTrials.gov. NCT06467539: Novel Augmentation of DAOIB and Antioxidant for Early Dementia (n.d.)
Unknown, Memantine for dementia? The Lancet Neurology (2006)PMID: 17012390(https://pubmed.ncbi.nlm.nih.gov/17012390/)
Unknown, Antioxidant therapy in Alzheimer disease. Neurology (2005)PMID: 15668448(https://pubmed.ncbi.nlm.nih.gov/15668448/)