DAOIBplusAO Phase 2 (NCT06467539) - Novel Antioxidant Augmentation for Early Dementia

DAOIBplusAO Phase 2 (NCT06467539): Novel NMDA-Enhancing Agent with Antioxidant Augmentation

Overview

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

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.

Trial Information

| 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

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

• 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:

Importance 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