scholarly journals Azathioprine immunosuppression and disease modification in Parkinson’s disease (AZA-PD): a randomised double-blind placebo-controlled phase II trial protocol

BMJ Open ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. e040527
Author(s):  
Julia C Greenland ◽  
Emma Cutting ◽  
Sonakshi Kadyan ◽  
Simon Bond ◽  
Anita Chhabra ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Immune System ◽  
Phase Ii ◽  
Rating Scale ◽  
Positron Emission Tomography Imaging ◽  
Clinical Markers ◽  
Double Blind ◽  
Positron Emission ◽  
Immunosuppressant Medication

IntroductionThe immune system is implicated in the aetiology and progression of Parkinson’s disease (PD). Inflammation and immune activation occur both in the brain and in the periphery, and a proinflammatory cytokine profile is associated with more rapid clinical progression. Furthermore, the risk of developing PD is related to genetic variation in immune-related genes and reduced by the use of immunosuppressant medication. We are therefore conducting a ‘proof of concept’ trial of azathioprine, an immunosuppressant medication, to investigate whether suppressing the peripheral immune system has a disease-modifying effect in PD.Methods and analysisAZA-PD is a phase II randomised placebo-controlled double-blind trial in early PD. Sixty participants, with clinical markers indicating an elevated risk of disease progression and no inflammatory or immune comorbidity, will be treated (azathioprine:placebo, 1:1) for 12 months, with a further 6-month follow-up. The primary outcome is the change in the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale gait/axial score in the OFF state over the 12-month treatment period. Exploratory outcomes include additional measures of motor and cognitive function, non-motor symptoms and quality of life. In addition, peripheral and central immune markers will be investigated through analysis of blood, cerebrospinal fluid and PK-11195 positron emission tomography imaging.Ethics and disseminationThe study was approved by the London-Westminster research ethics committee (reference 19/LO/1705) and has been accepted by the Medicines and Healthcare products Regulatory Agency (MHRA) for a clinical trials authorisation (reference CTA 12854/0248/001–0001). In addition, approval has been granted from the Administration of Radioactive Substances Advisory Committee. The results of this trial will be disseminated through publication in scientific journals and presentation at national and international conferences, and a lay summary will be available on our website.Trial registration numbersISRCTN14616801 and EudraCT- 2018-003089-14.

scholarly journals A Randomized Controlled Trial of Chinese Medicine on Nonmotor Symptoms in Parkinson’s Disease

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Ka-Kit Chua ◽  
Adrian Wong ◽  
Kam-Wa Chan ◽  
Yin-Kei Lau ◽  
Zhao-Xiang Bian ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Chinese Medicine ◽  
Rating Scale ◽  
Controlled Trial ◽  
Nonmotor Symptoms ◽  
Double Blind ◽  
Term Administration ◽  
Post Hoc ◽  
Chinese Medicine Theory

Nonmotor symptoms (NMS) of Parkinson’s disease (PD) have devastating impacts on both patients and their caregivers. Jiawei-Liujunzi Tang (JLT) has been used to treat some NMS of PD based on the Chinese medicine theory since Qing dynasty. Here we report a double-blind, randomized, placebo-controlled, add-on clinical trial aiming at evaluating the efficacy and safety of the JLT in treating NMS in PD patients. We randomly assigned 111 patients with idiopathic PD to receive either JLT or placebo for 32 weeks. Outcome measures were baseline to week 32 changes in Movement Disorder Society-Sponsored Revision of Unified PD Rating Scale (MDS-UPDRS) Parts I–IV and in NMS assessment scale for PD (NMSS). We observed improvements in the NMSS total score (p=0.019), mood/cognition (p=0.005), and reduction in hallucinations (p=0.024). In addition, post hoc analysis showed a significant reduction in constipation (p<0.001). However, there was no evidence of improvement in MDS-UPDRS Part I total score (p=0.216) at week 32. Adverse events (AEs) were mild and comparable between the two groups. In conclusion, long-term administration of JLT is well tolerated and shows significant benefits in improving NMS including mood, cognition, and constipation.

scholarly journals Efficacy and safety of rasagiline as an adjunct to levodopa treatment in Chinese patients with Parkinson's disease: a randomized, double-blind, parallel-controlled, multi-centre trial

2013 ◽  
Vol 16 (7) ◽  
pp. 1529-1537 ◽  
Author(s):  
Lina Zhang ◽  
Zhiqin Zhang ◽  
Yangmei Chen ◽  
Xinyue Qin ◽  
Huadong Zhou ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rating Scale ◽  
Chinese Patients ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Levodopa Treatment ◽  
Parallel Group ◽  
Disease Rating ◽  
Rasagiline Mesylate

Abstract Rasagiline mesylate is a highly potent, selective and irreversible monoamine oxidase type B (MAOB) inhibitor and is effective as monotherapy or adjunct to levodopa for patients with Parkinson's disease (PD). However, few studies have evaluated the efficacy and safety of rasagiline in the Chinese population. This study was designed to investigate the safety and efficacy of rasagiline as adjunctive therapy to levodopa treatment in Chinese PD patients. This was a randomized, double-blind, placebo-controlled, parallel-group, multi-centre trial conducted over a 12-wk period that enrolled 244 PD patients with motor fluctuations. Participants were randomly assigned to oral rasagiline mesylate (1 mg) or placebo, once daily. Altogether, 219 patients completed the trial. Rasagiline showed significantly greater efficacy compared with placebo. During the treatment period, the primary efficacy variable – mean adjusted total daily off time – decreased from baseline by 1.7 h in patients treated with 1.0 mg/d rasagiline compared to placebo (p < 0.05). Scores using the Unified Parkinson's Disease Rating Scale also improved during rasagiline treatment. Rasagiline was well tolerated. This study demonstrated that rasagiline mesylate is effective and well tolerated as an adjunct to levodopa treatment in Chinese PD patients with fluctuations.

scholarly journals Evaluation of the safety and immunomodulatory effects of sargramostim in a randomized, double-blind phase 1 clinical Parkinson’s disease trial

2017 ◽  
Vol 3 (1) ◽  
Author(s):  
Howard E. Gendelman ◽  
Yuning Zhang ◽  
Pamela Santamaria ◽  
Katherine E. Olson ◽  
Charles R. Schutt ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rating Scale ◽  
Clinical Investigation ◽  
Phase 1 ◽  
Additional Patient ◽  
Double Blind ◽  
Modest Improvement ◽  
Cell Counts ◽  
Study Results

Abstract A potential therapeutic role for immune transformation in Parkinson’s disease evolves from more than a decade of animal investigations demonstrating regulatory T cell (Treg) nigrostriatal neuroprotection. To bridge these results to human disease, we conducted a randomized, placebo-controlled double-blind phase 1 trial with a well-studied immune modulator, sargramostim (granulocyte-macrophage colony-stimulating factor). We enrolled 17 age-matched non-Parkinsonian subjects as non-treated controls and 20 Parkinson’s disease patients. Both Parkinson’s disease patients and controls were monitored for 2 months for baseline profiling. Parkinson’s disease patients were then randomized into two equal groups to self-administer placebo (saline) or sargramostim subcutaneously at 6 μg/kg/day for 56 days. Adverse events for the sargramostim and placebo groups were 100% (10/10) and 80% (8/10), respectively. These included injection site reactions, increased total white cell counts, and upper extremity bone pain. One urticarial and one vasculitis reaction were found to be drug and benzyl alcohol related, respectively. An additional patient with a history of cerebrovascular disease suffered a stroke on study. Unified Parkinson’s disease rating scale, Part III scores in the sargramostim group showed modest improvement after 6 and 8 weeks of treatment when compared with placebo. This paralleled improved magnetoencephalography-recorded cortical motor activities and Treg numbers and function compared with pretreated Parkinson’s disease patients and non-Parkinsonian controls. Peripheral Treg transformation was linked to serum tryptophan metabolites, including L-kynurenine, quinolinic acid, and serotonin. These data offer a potential paradigm shift in modulating immune responses for potential therapeutic gain for Parkinson’s disease. Confirmation of these early study results requires larger numbers of enrolled patients and further clinical investigation.

scholarly journals Low dose niacin versus placebo in the treatment of Parkinson’s Disease:  A Randomized Controlled Trial

2021 ◽  
Author(s):  
Chandramohan Wakade ◽  
Raymond Chong ◽  
Marissa Seamon ◽  
Sharad Purohit ◽  
Banabihari Giri ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Low Dose ◽  
Rating Scale ◽  
Controlled Trial ◽  
Secondary Outcome ◽  
Open Label ◽  
Double Blind ◽  
One Year ◽  
Time Point

Abstract BackgroundParkinson’s Disease (PD) patients have lower niacin levels compared to their spouses. The main objective was to study low-dose daily niacin supplementation versus placebo on motor symptoms in Parkinson’s disease subjects.MethodsA randomized, placebo-controlled, double-blind, single-center clinical trial in Parkinson’s disease patients was performed in Augusta, GA, between September 2016 to September 2019. Randomized participants were 47 PD patients who received either low-dose niacin (N = 21 ) or placebo (N = 26) for the first six months (mean age 68.4 SD, 8.7; mean duration of disease 5.8 SD 4.9; H&Y scores between 0.5 to 4; 64% subjects were Veterans). The Veterans Affairs Pharmacy generated the randomized sequence. After the double-blind phase, all participants received open-label niacin for the next six months. All patients were evaluated at baseline, six months, and one year of treatment. The main outcome measure was the Unified Parkinson’s Disease Rating Scale III (UPDRS III) scores. Secondary outcome measures were depression, sleep quality, mental flexibility and cognition, and physical fatigue.Results39 subjects were analyzed with low-dose niacin (N = 18) and placebo (N = 21) for the completion of the first six months (randomized, double-blind), and 31 subjects were analyzed for the completion of the next six months (open-label) with low-dose niacin (N = 14) and placebo (N = 17). Niacin treatment was not tolerated by two subjects. The baseline mean UPDRS III score was 21.3 ± 15.8 for the niacin group and 22.4 ± 11.8 for placebo. The change with six months of placebo was 0.05 [95% CI, -2.4 to 2.32], and niacin was 1.06 [95% CI, -3.68 to 1.57]. From six to twelve months, the average UPDRS III score decreased for the placebo group by 4.58 [95% CI, -0.85 to 8.30] and the niacin group by 4.63 [95% CI, 1.42 to 7.83]. Eight subjects withdrew from the study before the 6-month time point and eight more before the one-year time point due to voluntary discontinuation, flushing, or inability to continue (SARS-CoV-2 shut-down).ConclusionLow-dose niacin supplementation may be helpful as an adjunct therapy in improving motor function in PD.Trial registrationClinicaltrials.gov, NCT03462680. Registered 12 March 2018- Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03462680?term=gpr109A&draw=2&rank=1

scholarly journals Metabolic network as an objective biomarker in monitoring deep brain stimulation for Parkinson’s disease: a longitudinal study

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Jingjie Ge ◽  
Min Wang ◽  
Wei Lin ◽  
Ping Wu ◽  
Yihui Guan ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Deep Brain Stimulation ◽  
Metabolic Network ◽  
Brain Stimulation ◽  
Rating Scale ◽  
Clinical Trial Registration ◽  
Positron Emission ◽  
Stn Dbs ◽  
Deep Brain

Abstract Background With the advance of subthalamic nucleus (STN) deep brain stimulation (DBS) in the treatment of Parkinson’s disease (PD), it is desired to identify objective criteria for the monitoring of the therapy outcome. This paper explores the feasibility of metabolic network derived from positron emission tomography (PET) with 18F-fluorodeoxyglucose in monitoring the STN DBS treatment for PD. Methods Age-matched 33 PD patients, 33 healthy controls (HCs), 9 PD patients with bilateral DBS surgery and 9 controls underwent 18F-FDG PET scans. The DBS patients were followed longitudinally to investigate the alternations of the PD-related metabolic covariance pattern (PDRP) expressions. Results The PDRP expression was abnormally elevated in PD patients compared with HCs (P < 0.001). For DBS patients, a significant decrease in the Unified Parkinson’s Disease Rating Scale (UPDRS, P = 0.001) and PDRP expression (P = 0.004) was observed 3 months after STN DBS treatment, while a rollback was observed in both UPDRS and PDRP expressions (both P < 0.01) 12 months after treatment. The changes in PDRP expression mediated by STN DBS were generally in line with UPDRS improvement. The graphical network analysis shows increased connections at 3 months and a return at 12 months confirmed by small-worldness coefficient. Conclusions The preliminary results demonstrate the potential of metabolic network expression as complimentary objective biomarker for the assessment and monitoring of STN DBS treatment in PD patients. Clinical Trial Registration ChiCTR-DOC-16008645. http://www.chictr.org.cn/showproj.aspx?proj=13865.

Positron emission tomography imaging of 5-hydroxytryptamine1B receptors in Parkinson's disease

2014 ◽  
Vol 35 (4) ◽  
pp. 867-875 ◽  
Author(s):  
Andrea Varrone ◽  
Per Svenningsson ◽  
Anton Forsberg ◽  
Katarina Varnäs ◽  
Mikael Tiger ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Positron Emission Tomography ◽  
Parkinson's Disease ◽  
Positron Emission Tomography Imaging ◽  
Emission Tomography ◽  
Tomography Imaging ◽  
Positron Emission

scholarly journals Preliminary finding of a randomized, double-blind, placebo-controlled, crossover study to evaluate the safety and efficacy of 5-hydroxytryptophan on REM sleep behavior disorder in Parkinson’s disease

2021 ◽  
Author(s):  
Mario Meloni ◽  
Michela Figorilli ◽  
Manolo Carta ◽  
Ludovica Tamburrino ◽  
Antonino Cannas ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rem Sleep ◽  
Rating Scale ◽  
Sleep Onset ◽  
Rem Sleep Behavior Disorder ◽  
Behavior Disorder ◽  
Double Blind ◽  
Sleep Behavior ◽  
Double Blind Placebo

Abstract Purpose Altered serotonergic neurotransmission may contribute to the non-motor features commonly associated with Parkinson’s disease (PD) such as sleep disorders. The 5-hydroxytryptophan (5-HTP) is the intermediate metabolite of l-tryptophan in the production of serotonin and melatonin. The purpose of this study was to compare the effects of 5-HTP to placebo on REM sleep behavior disorder (RBD) status in patients with PD. Methods A single-center, randomized, double-blind placebo-controlled crossover trial was performed in a selected population of 18 patients with PD and RBD. The patients received a placebo and 50 mg of 5-HTP daily in a crossover design over a period of 4 weeks. Results 5-HTP produced an increase in the total percentage of stage REM sleep without a related increase of RBD episodes, as well as a marginal, non-significant reduction in both arousal index and wake after sleep onset. The self-reported RBD frequency and clinical global impression (CGI) were improved during 5-HTP and placebo treatment in comparison to baseline. 5-HTP significantly improved our patients’ motor experiences of daily living as rated by the Unified Parkinson’s Disease Rating Scale (UPDRS) part II. Conclusions This study provides evidence that 5-HTP is safe and effective in improving sleep stability in PD, contributing to ameliorate patients’ global sleep quality. Larger studies with higher doses and longer treatment duration are needed to corroborate these preliminary findings.

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