| Field |
Value |
| NCT Number |
NCT07055958 |
| Title |
Metformin Add-on Therapy for Parkinson's Disease |
| Status |
Recruiting |
| Phase |
Phase II |
| Condition(s) |
Parkinson's Disease |
| Intervention |
Metformin hydrochloride 500mg twice daily + standard Levodopa/Carbidopa |
| Sponsor |
Bangabandhu Sheikh Mujib Medical University, Bangladesh |
| Location |
Dhaka, Bangladesh |
| Enrollment |
60 patients (estimated) |
| Study Duration |
52 weeks |
This Phase II clinical trial investigates the efficacy and safety of metformin as an add-on therapy to standard Levodopa/Carbidopa treatment in patients with Parkinson's disease. The study is conducted at Bangabandhu Sheikh Mujib Medical University (BSMMU) in Dhaka, Bangladesh[@bsfmu].
Metformin, a widely used antidiabetic medication, has shown significant neuroprotective potential in preclinical models of Parkinson's disease through multiple mechanisms:
-
AMPK Activation: Metformin activates AMP-activated protein kinase (AMPK), which promotes autophagy and enhances clearance of alpha-synuclein aggregates[@metforminautophagy2022]
-
Mitochondrial Protection: The drug improves mitochondrial function, reduces oxidative stress, and protects dopaminergic neurons from degeneration[@metforminpd2021]
-
Anti-inflammatory Effects: Metformin reduces neuroinflammation by modulating microglial activation and decreasing pro-inflammatory cytokines
-
Blood-Brain Barrier Penetration: Metformin has demonstrated ability to cross the BBB and exert direct effects on brain cells
- Primary: Metformin add-on therapy will improve motor symptoms (MDS-UPDRS Part III) compared to Levodopa/Carbidopa alone
- Secondary: Metformin will reduce non-motor symptoms and improve quality of life measures
- Diagnosis of idiopathic Parkinson's disease (UK Brain Bank criteria)
- Hoehn & Yahr stage 2-3
- On stable Levodopa/Carbidopa therapy for ≥3 months
- Age 40-75 years
- Ability to provide informed consent
- Diabetes mellitus (prior or current)
- Severe renal or hepatic impairment
- Previous metformin use
- History of lactic acidosis
- Cognitive impairment (MMSE <24)
| Arm |
Intervention |
Description |
| Active |
Metformin 500mg BID + Levodopa/Carbidopa |
Experimental arm |
| Control |
Placebo + Levodopa/Carbidopa |
Standard of care |
- Change in MDS-UPDRS Part III (motor) score at 52 weeks
- Change in "Off" time (hours) via patient diary
- Non-motor symptom assessment (NMSS)
- Quality of life (PDQ-39)
- MoCA (cognitive function)
- Hospital Anxiety and Depression Scale (HADS)
- Adverse events and safety monitoring
Metformin exerts neuroprotective effects through several interconnected pathways:
flowchart TD
A["Metformin"] --> B["Mitochondrial Complex I Inhibition"]
B --> C["AMP/ATP Ratio Increase"]
C --> D["AMPK Activation"]
D --> E["Multiple Neuroprotective Effects"]
E --> E1["ULK1 Activation → Autophagy"]
E --> E2["mTORC1 Inhibition"]
E --> E3["PGC-1α → Mitochondrial Biogenesis"]
E --> E4["NLRP3 Inhibition → Anti-inflammatory"]
E1 --> F["α-Synuclein Clearance"]
E2 --> G["Protein Synthesis Regulation"]
E3 --> H["Mitochondrial Function"]
E4 --> I["Neuroinflammation Reduction"]
F --> J["Dopaminergic Neuron Protection"]
G --> J
H --> J
I --> J
| Target |
Effect |
Relevance to PD |
| AMPK |
Activation |
Promotes autophagy, inhibits mTOR |
| mTOR |
Inhibition |
Reduces protein aggregation |
| PGC-1α |
Activation |
Mitochondrial biogenesis |
| NLRP3 |
Inhibition |
Reduces neuroinflammation |
| α-Synuclein |
Clearance |
Reduces toxic aggregates |
Metformin has been extensively studied in both Alzheimer's and Parkinson's disease. Meta-analyses suggest:
- Reduced PD Risk: Observational studies show 30-40% reduced risk of PD in metformin users with type 2 diabetes[@metformindm2023]
- Motor Progression: Retrospective studies indicate slower motor progression in PD patients using metformin
- Synergistic Effects: Combination with Levodopa may enhance dopaminergic function
| Trial |
Intervention |
Phase |
Status |
| NCT01971242 |
Exenatide |
Phase 2 |
Completed |
| NCT03025269 |
Exenatide |
Phase 3 |
Completed |
| NCT04616348 |
Metformin + Diabetes |
Phase 3 |
Recruiting |
| NCT07055958 |
Metformin + Levodopa |
Phase 2 |
Recruiting |
¶ Risks and Safety Considerations
- Gastrointestinal: nausea, diarrhea, abdominal discomfort
- Usually transient and manageable
- Lactic acidosis (contraindicated in renal impairment)
- Vitamin B12 deficiency (long-term use)
- Hypoglycemia (when combined with insulinsecretagogues)
- Baseline renal function (eGFR)
- Liver function tests
- Fasting glucose
- Vitamin B12 levels (if prolonged use)
¶ Bangabandhu Sheikh Mujib Medical University (BSMMU)
BSMMU is Bangladesh's premier medical research institution, located in Dhaka. The university conducts clinical research across multiple therapeutic areas, including neurology and neurodegenerative diseases. This trial represents an important effort to bring innovative therapeutic approaches to patients in South Asia.
This trial addresses several key questions:
- Repurposing Potential: Can an established diabetes drug provide disease-modifying benefits in PD?
- Population Diversity: Does the neuroprotective effect generalize to South Asian populations?
- Combination Therapy: Is metformin + Levodopa superior to Levodopa alone?
Positive results from this trial could:
- Establish metformin as a low-cost neuroprotective option for PD
- Inform larger Phase 3 trials in diverse populations
- Support combination therapy approaches
- Provide evidence for metformin use in early PD
- NCT07055958: Metformin add-on to Levodopa for Parkinson's Disease
- Metformin and Parkinson's disease: a potential disease-modifying therapy (2023)
- Metformin: a potential neuroprotective agent in Parkinson's disease (2022)
- Metformin prevents dopaminergic neuron death through AMPK activation (2021)
- Bangabandhu Sheikh Mujib Medical University