Reduction of Tinnitus Severity by the Centrally Acting Muscle Relaxant Cyclobenzaprine: An Open-Label Pilot Study

BACKGROUND The precise mechanisms whereby cardiovascular risk factors increase the risk of Alzheimer’s disease (AD) have not been delineated. We reported that microvessels isolated from AD brains overexpress a diverse array of neurotoxic and inflammatory proteins, which is consistent with the process of vascular activation. In pre-clinical studies using AD animal models we showed that a vascular activation inhibitor reduced vascular-derived neuroinflammation and improved cognitive performance. Thrombin is a key mediator of cerebrovascular activation in AD. OBJECTIVE This study aims to investigate the safety and potential efficacy of the direct thrombin inhibitor dabigatran, in patients with mild cognitive impairment (MCI) or mild AD to decrease vascular-derived neuroinflammation and improve cognitive performance. METHODS Participants will be enrolled then evaluated quarterly throughout the 24-month study. This is a 24-month randomized-control, double-blind, placebo-controlled, multicenter, delayed-start, pilot study evaluating thrombin inhibition in people with biomarker-confirmed MCI probably due to AD or mild AD. 40 - 60 participants will be recruited between 50 - 85 years old. In the initial 9-months of study, either dabigatran or placebo will be orally administered to patients at a dose of 150 mg per day. After 9 months of the placebo-control (Phase I), the placebo arm will cross-over to an active, open-label (Phase II) where all patients will be treated with a 150 mg daily dose of dabigatran orally for an additional 12 months. A 3-month non-treatment follow-up period will assess duration of effects. RESULTS Beginning in July 2019, and concluding in August 2022, this study is expected to publish final results in January 2023. CONCLUSIONS BEACON is a first-in-kind randomized clinical trial targeting thrombin activation in AD therapeutics. This trial will stimulate translational investigations of an FDA-approved drugs in a newly defined therapeutic areas. CLINICALTRIAL Clinicaltrials.gov NCT03752294

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An open-label, single-center pilot study to test the effects of an amino acid mixture in older patients admitted to internal medicine wards

Nutrition ◽

10.1016/j.nut.2019.110588 ◽

2020 ◽

Vol 69 ◽

pp. 110588 ◽

Cited By ~ 1

Author(s):

Francesco Bellanti ◽

Aurelio Lo Buglio ◽

Elena Di Stasio ◽

Giorgia di Bello ◽

Rosanna Tamborra ◽

...

Keyword(s):

Internal Medicine ◽

Amino Acid ◽

Pilot Study ◽

Older Patients ◽

Amino Acid Mixture ◽

Acid Mixture ◽

Single Center ◽

Open Label ◽

Internal Medicine Wards

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Effects of bumetanide on neurodevelopmental impairments in patients with tuberous sclerosis complex: an open-label pilot study

Molecular Autism ◽

10.1186/s13229-020-00335-4 ◽

2020 ◽

Vol 11 (1) ◽

Cited By ~ 2

Author(s):

Dorinde M. van Andel ◽

Jan J. Sprengers ◽

Bob Oranje ◽

Floortje E. Scheepers ◽

Floor E. Jansen ◽

...

Keyword(s):

Pilot Study ◽

Tuberous Sclerosis ◽

Tuberous Sclerosis Complex ◽

Open Label

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EVALUATION OF A DIET AND ANTIBIOTICS TARGETING THE MICROBIOTA FOR TREATMENT OF MILD TO MODETARE ACTIVE PEDIARTIC ULCERATIVE COLITIS: AN OPEN LABEL PILOT STUDY

Inflammatory Bowel Diseases ◽

10.1093/ibd/izaa347.094 ◽

2021 ◽

Vol 27 (Supplement_1) ◽

pp. S38-S38

Author(s):

Chen Sarbagili-Shabat ◽

Lindsey Albenberg ◽

Johan Van Limbergen ◽

Dror Weiner ◽

Michal Yaakov ◽

...

Keyword(s):

Ulcerative Colitis ◽

Pilot Study ◽

Dietary Intervention ◽

Activity Index ◽

Fecal Calprotectin ◽

Dietary Therapy ◽

The Novel ◽

Open Label ◽

Intention To Treat ◽

Stable Maintenance

Abstract Background Newer strategies that target the microbiome may offer an alternative therapeutic approach for Ulcerative Colitis (UC). We developed a novel diet that targets changes in the microbiome and barrier function that have been reported in UC. The goal of the current study was to evaluate the efficacy of two sequential induction of remission strategies that target the microbiota: the novel diet termed the ulcerative colitis diet (UCD) and an antibiotics cocktail combination in dietary non responders. Methods This was a prospective, single arm, open label, pilot study in patients aged 8–19, with a pediatric UC activity index (PUCAI) scores >10 and ≤45 on stable maintenance therapy (5ASA or thiopurines). PUCAI score was assessed at week 3 and 6. Patients failing to enter remission or intolerant to dietary therapy could receive an open label 14-day course of Amoxycillin, Metronidazole and Doxycycline (AMD), and had PUCAI scored at day 21. Response was defined a decline in PUCAI ≥ 10 points, remission as PUCAI< 10. The primary endpoint was intention to treat (ITT) remission at week 6 with diet as the sole intervention. Results Twenty-three children mean age of 15.1±2.9 years were enrolled. Two patients (1 responder, 1 remission) withdrew by 3 weeks, four required additional therapy by week 3, all were considered failures by ITT. Mean PUCAI decreased at week 3 and 6 from 34.5±9.8 to 21.7±14.9 and 17.6±17.2 respectively (P=0.005, P=0.001) at ITT analysis including all patients. Sixteen out of twenty-three patients (69.6%) responded by week 6. Ten of twenty-three (43.5%) achieved remission by week 6, and nine (39.1%) had clinical remission at week 6. The median fecal calprotectin (FC) level decreased in patients (n=5) who achieved remission from 630 (IQR, 332–1586) μg/g at week 0 to 230 (75–1298) μg/g at week 6. Eight patients received treatment with antibiotics after failing diet, 4/8 (50.0%) subsequently entered remission. Conclusion A dietary intervention called the UC Diet appears to be effective for induction of remission in children with mild to moderate UC. Sequential use of diet, followed by antibiotic therapy in dietary non responders, needs further evaluation as a microbiome directed steroid sparing therapy in patient’s refractory to 5ASA and thiopurines.

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