Mild Cognitive Impairment (MCI)
Conditions
Keywords
Mild Cognitive Impairment (MCI), Tadalafil
Brief summary
The goal of this clinical trial is to determine if taking four weeks of a daily low dose of tadalafil is possible and safe in elderly males and females with mild cognitive impairment. Additionally, we aim to determine if this drug that improves blood flow can improve cognition and functionality of the blood vessels in the brain. The main questions the trial aims to answer are: 1. Will elderly patients with mild cognitive impairment be able to tolerate taking a daily, low dose (5 mg) of tadalafil? 2. Does 5 mg of daily tadalafil improve cerebral vasomotor reactivity (i.e. vascular function) and cognition? Participants will to: 1. Answer questions about your health 2. Take three short thinking and memory tests 3. Have your blood pressure and heart rate checked 4. Have an electrocardiogram 5. Fill out a thinking questionnaire 6. Fill out a suicidality questionnaire 7. Have a brain blood flow test 8. Get three blood tests throughout the study 9. Take tadalafil once daily 10. Monitor your blood pressure twice daily 11. Record any side effects 12. Return after 4 weeks and repeat testing
Interventions
DRUGTadalafil 5 mg
Participants will take a daily dose of 5 mg of tadalafil over a 4 week period
Sponsors
Los Angeles Brain Science Project
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
60 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* The participant is between the ages of 60-90 years old. * The participant must demonstrate a MoCA score ≥ 18 and ≤ 25. * The participant has consented for his/herself. * The participant has a caregiver, family member, or qualified individual to help with study tasks * The participant is fluent in the English language. * The participant is proficient in comprehending verbal and written English.
Exclusion criteria
1. Any of the aforementioned CMP values meet the exclusion threshold. 2. Absence of a caregiver, family member, or other appropriately qualified individual that will be available for the entire experimental duration to assist the participant with study tasks, including supervision of medication intake, recording blood pressure, and noting adverse events. 3. Current use of any form of organic nitrates or nitrite-containing medications, or planned nitrate use within 48 hours of tadalafil dosing. 4. Known hypersensitivity to tadalafil or to any component of the formulation. 5. Recent (within prior 3 months) acute cardiovascular events - e.g., myocardial infarction, unstable angina, stroke, or life-threatening cardiac arrhythmia - or decompensated/unstable heart failure according to the New York Heart Association (NYHA) class II-IV. 6. Resting hypotension (systolic BP \<90 mmHg) or clinically significant symptomatic orthostatic hypotension, or uncontrolled severe hypertension (e.g., systolic BP \>170 mmHg or diastolic BP \>110 mmHg). 7. Concurrent use of potent CYP3A4 inhibitors, including but not limited to: i. Amiodarone ii. Aprepitant iii. Azamulin iv. Cimetidine v. Ciprofloxacin vi. Clarithromycin vii. Diltiazem viii. Erythromycin ix. Fedratiib x. Fedratinib xi. Fluconazole xii. Itraconazole xiii. Ketoconazole xiv. Letermovir xv. Nirmatrelvir-Ritonavir xvi. Posaconazole xvii. Troleandomycin xviii. Voriconazole xix. Verapamil xx. Grapefruit and Grapefruit Juice xxi. Seville Orange Juice xxii. Pomelo Juice xxiii. Green tea extract xxiv. Curcumin/tumeric xxv. Black pepper extract xxvi. Goldenseal xxvii. Gingko Biloba xxviii. Kava xxix. Kratom xxx. CBD oil xxxi. Ginger xxxii. Elderberry Extract 8. Concurrent use of alpha-adrenergic blockers (unless on a stable dose and the investigator documents that coadministration is acceptable and that BP monitoring and dosing separation strategies are in place). 9. Severe renal impairment or end-stage renal disease (ESRD) on hemodialysis, and other renal dysfunction that, per the tadalafil product labeling, would contraindicate or require specific dosing changes for the intended tadalafil regimen. 10. Documented hepatic impairment, defined by Child Pugh Class A, B, or C. 11. History of non-arteritic anterior ischemic optic neuropathy (NAION), prior vision loss attributed to a PDE-5 inhibitor, or hereditary retinal disorders (e.g., retinitis pigmentosa). 12. Conditions that predispose to priapism (e.g., sickle cell disease, multiple myeloma, leukemia) if sexually active participants are at risk from prolonged erections. 13. Medical, neurologic, or psychiatric conditions (including advanced dementia) that, in the investigator's judgment, would preclude safe participation, study compliance, or the ability to provide informed consent. 14. Participants on guanylate cyclase (GS) stimulators such as riociguat (Adempas) 15. Participants with left ventricular outflow obstruction (e.g. aortic stenosis, idiopathic hypertrophic subaortic stenosis). 16. Participants with severe autonomic dysfunction. 17. Participants with known or suspected pulmonary veno-occlusive disease. 18. Participants with known hereditary degenerative retinal disorders, including retinitis pigmentosa, and those with underlying non-arteritic anterior ischemic optic neuropathy (NAION) risk factors. 19. Participants with active peptic ulceration or significant bleeding disorders. 20. Participants on other phosphodiesterase-5 (PDE5) inhibitors (sildenafil, vardenafil, avanafil). 21. Participants with an anatomical deformation of the penis (such as angulation, cavernosal fibrosis, or Peyronie's disease). 22. Participants with any uncontrolled arrhythmia, as determined by the screening electrocardiogram. 23. Participants with a creatinine clearance less than 30 mL/min. 24. Participants with a history of substantial alcohol consumption (≥ 5 units per day)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Compliance (%) with tadalafil | From beginning to the end of treatment at four weeks | Assessed as the value equal to 100 x (number of dispensed tablets - returned tablets) / (planned days on trial medication) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cerebrovascular Reactivity to Hypercapnia | Baseline (pre-) and post-intervention at 4 weeks | Measured using transcranial doppler ultrasonography (TCD) of the bilateral middle cerebral arteries and breath-holding test (BHT) techniques |
| Resting Heart Rate | Resting heart rate measured at baseline (pre-) and post-intervention at 4 weeks | Resting heart rate (bpm) measured using the OMRON BP7000 Evolv Upper Arm monitor |
| Blood Pressure | Baseline, twice daily throughout the study (i.e. 4 weeks), and post-intervention at 4 weeks | Blood pressure (mmHg) measured using the OMRON BP7000 Evolv Upper Arm monitor |
| Neurocognitive Testing | Baseline (pre-) and post-intervention at 4 weeks | 1. Fatigue and Altered Cognition Scale (FACs) - 20 item questionnaire equally divided into 10 categories designed to determine altered cognition and another 10 categories to assess central fatigue within the previous two weeks. Each item operates under a 0 (not at all) - 100 (extremely), with higher scores indicating feeling more aligned with the statement or symptom(s). 2. Creyos Cognitive Assessment - brief assessment of attention, mental rotation, deductive and verbal reasoning, and visuospatial and episodic memory. Each domain is graded on a sex- and age-specific standardized scale with no fixed minimum or maximum value. Distributions operate with a mean score = 100 and standard deviation = 15. Demographic-specific scales are used to describe the results, including scores ≤ 87 described as "Below average," scores ≥ 113 described as "Above average," and all scores between these two bounds described as "Average." |
| Adverse Events | During the intervention period | Any and all adverse side-effects experienced while taking tadalafil will be documented using a written paper-based log. Summarization of adverse events, characterized by frequency and severity, will be facilitated |
Countries
United States
Contacts
CONTACTTrent Yamamoto, MS
PRINCIPAL_INVESTIGATORDaniel Franc, MD, PhD
Los Angeles Brain Science Project
Outcome results
None listed