Caffeine as symptomatic treatment for Parkinson disease (Cafe-PD): A randomized trial.
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ABSTRACT: Objective
To assess effects of caffeine on Parkinson disease (PD).Methods
In this multicenter parallel-group controlled trial, patients with PD with 1-8 years disease duration, Hoehn & Yahr stages I-III, on stable symptomatic therapy were randomized to caffeine 200 mg BID vs matching placebo capsules for 6-18 months. The primary research question was whether objective motor scores would differ at 6 months (Movement Disorder Society-sponsored Unified Parkinson's Disease Rating Scale [MDS-UPDRS]-III, Class I evidence). Secondary outcomes included safety and tolerability, motor symptoms (MDS-UPDRS-II), motor fluctuations, sleep, nonmotor symptoms (MDS-UPDRS-I), cognition (Montreal Cognitive Assessment), and quality of life.Results
Sixty patients received caffeine and 61 placebo. Caffeine was well-tolerated with similar prevalence of side effects as placebo. There was no improvement in motor parkinsonism (the primary outcome) with caffeine treatment compared to placebo (difference between groups -0.48 [95% confidence interval -3.21 to 2.25] points on MDS-UPDRS-III). Similarly, on secondary outcomes, there was no change in motor signs or motor symptoms (MDS-UPDRS-II) at any time point, and no difference on quality of life. There was a slight improvement in somnolence over the first 6 months, which attenuated over time. There was a slight increase in dyskinesia with caffeine (MDS-UPDRS-4.1+4.2 = 0.25 points higher), and caffeine was associated with worse cognitive testing scores (average Montreal Cognitive Assessment = 0.66 [0.01, 1.32] worse than placebo).Conclusion
Caffeine did not provide clinically important improvement of motor manifestations of PD (Class I evidence). Epidemiologic links between caffeine and lower PD risk do not appear to be explained by symptomatic effects.Clinicaltrialsgov identifier
NCT01738178.Classification of evidence
This study provides Class I evidence that for patients with PD, caffeine does not significantly improve motor manifestations.
SUBMITTER: Postuma RB
PROVIDER: S-EPMC5664303 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveEpidemiologic studies consistently link caffeine, a nonselective adenosine antagonist, to lower risk of Parkinson disease (PD). However, the symptomatic effects of caffeine in PD have not been adequately evaluated.MethodsWe conducted a 6-week randomized controlled trial of caffeine in PD to assess effects upon daytime somnolence, motor severity, and other nonmotor features. Patients with PD with daytime somnolence (Epworth >10) were given caffeine 100 mg twice daily ×3 weeks, then 200 mg twice daily ×3 weeks, or matching placebo. The primary outcome was the Epworth Sleepiness Scale score. Secondary outcomes included motor severity, sleep markers, fatigue, depression, and quality of life. Effects of caffeine were analyzed with Bayesian hierarchical models, adjusting for study site, baseline scores, age, and sex.ResultsOf 61 patients, 31 were randomized to placebo and 30 to caffeine. On the primary intention-to-treat analysis, caffeine resulted in a nonsignificant reduction in Epworth Sleepiness Scale score (-1.71 points; 95% confidence interval [CI] -3.57, 0.13). However, somnolence improved on the Clinical Global Impression of Change (+0.64; 0.16, 1.13, intention-to-treat), with significant reduction in Epworth Sleepiness Scale score on per-protocol analysis (-1.97; -3.87, -0.05). Caffeine reduced the total Unified Parkinson's Disease Rating Scale score (-4.69 points; -7.7, -1.6) and the objective motor component (-3.15 points; -5.50, -0.83). Other than modest improvement in global health measures, there were no changes in quality of life, depression, or sleep quality. Adverse events were comparable in caffeine and placebo groups.ConclusionsCaffeine provided only equivocal borderline improvement in excessive somnolence in PD, but improved objective motor measures. These potential motor benefits suggest that a larger long-term trial of caffeine is warranted.Classification of evidenceThis study provides Class I evidence that caffeine, up to 200 mg BID for 6 weeks, had no significant benefit on excessive daytime sleepiness in patients with PD.
| S-EPMC3414662 | biostudies-literature
Project description:Parkinson disease (PD), as a slowly progressive neurodegenerative disorder, undergoes six neuropathological stages. The earliest clinical manifestation presents in the middle stage of the disorder pathologically, when 50% or more of the dopaminergic neurons have degenerated in the substantia nigra. This discrepancy between the early stage clinically and that pathologically has, in part, spurred the debate as to when it is best to initiate symptomatic therapy. The most well-studied monotherapeutic agents for PD in its early course include levodopa (the cornerstone of PD therapy), dopamine agonists, and monoamine oxidase inhibitors (MAOIs). With several options for initiating pharmacologic therapy, along with the heterogenous presentation of the disorder, an individualized approach is warranted. Careful deliberation must be done to optimize risk reduction while providing effective symptom control, taking the chronological age, comorbidities, social and financial disposition, work status, and both immediate- and long-term goals into consideration. Generally, treatment can be delayed in patients with mild symptoms and minimal functional impairment at any age. If treatment must be initiated, dopamine agonists and monoamine oxidase type B inhibitors can be used, especially in younger patients with milder disease. However, for older patients, those with moderate to severe PD symptoms, regardless of age, or for patients with greater comorbidities, levodopa generally remains the better choice. Eventually, regardless of initial therapy, studies have shown that most will eventually require levodopa therapy when symptoms become more disabling.
| S-EPMC7851218 | biostudies-literature
Project description:In the present study, we examined the potential symptomatic and/or disease-modifying effects of monthly bee venom injections compared to placebo in moderatly affected Parkinson disease patients. We conducted a prospective, randomized double-blind study in 40 Parkinson disease patients at Hoehn & Yahr stages 1.5 to 3 who were either assigned to monthly bee venom injections or equivalent volumes of saline (treatment/placebo group: n = 20/20). The primary objective of this study was to assess a potential symptomatic effect of s.c. bee venom injections (100 ?g) compared to placebo 11 months after initiation of therapy on United Parkinson’s Disease Rating Scale (UPDRS) III scores in the « off » condition pre-and post-injection at a 60 minute interval. Secondary objectives included the evolution of UPDRS III scores over the study period and [123I]-FP-CIT scans to evaluate disease progression. Finally, safety was assessed by monitoring specific IgE against bee venom and skin tests when necessary. After an 11 month period of monthly administration, bee venom did not significantly decrease UPDRS III scores in the « off » condition. Also, UPDRS III scores over the study course, and nuclear imaging, did not differ significantly between treatment groups. Four patients were excluded during the trial due to positive skin tests but no systemic allergic reaction was recorded. After an initial increase, specific IgE against bee venom decreased in all patients completing the trial. This study did not evidence any clear symptomatic or disease-modifying effects of monthly bee venom injections over an 11 month period compared to placebo using a standard bee venom allergy desensitization protocol in Parkinson disease patients. However, bee venom administration appeared safe in non-allergic subjects. Thus, we suggest that higher administration frequency and possibly higher individual doses of bee venom may reveal its potency in treating Parkinson disease.ClinicalTrials.gov NCT01341431.
| S-EPMC4942057 | biostudies-literature
Project description:This study presents a secondary analysis from the Progressive Resistance Exercise Training in Parkinson Disease (PRET-PD) trial investigating the effects of progressive resistance exercise (PRE) and a Parkinson disease (PD)-specific multimodal exercise program, modified Fitness Counts (mFC), on spatial, temporal, and stability-related gait impairments in people with PD.Forty-eight people with PD were randomized to participate in PRE or mFC 2 times a week for 24 months; 38 completed the study. Gait velocity, stride length, cadence, and double-support time were measured under 4 walking conditions (off-/on-medication, comfortable/fast speed). Ankle strength was also measured off- and on-medication. Twenty-four healthy controls provided comparison data at one time point.At 24 months, there were no significant differences between exercise groups. Both groups improved fast gait velocity off-medication, cadence in all conditions, and plantarflexion strength off-/on-medication. Both groups with PD had more gait measures that approximated the healthy controls at 24 months than at baseline. Plantarflexion strength was significantly associated with gait velocity and stride length in people with PD at baseline and 24 months, but changes in strength were not associated with changes in gait.Twenty-four months of PRE and mFC were associated with improved off-medication fast gait velocity and improved cadence in all conditions, which is important because temporal gait measures can be resistant to medications. Spatial and stability-related measures were resistant to long-term improvements, but did not decline over 24 months. Strength gains did not appear to transfer to gait.Video Abstract available for more insights from the authors (see Supplemental Digital Content 1, http://links.lww.com/JNPT/A161).
| S-EPMC5161103 | biostudies-literature
Project description:OBJECTIVE:To evaluate the efficacy and safety of caffeine citrate in the treatment of apnea in bronchiolitis. STUDY DESIGN:Eligible infants aged ?4 months presenting to the main pediatric emergency service with apnea associated bronchiolitis were stratified by gestational age (<34 weeks or longer) and randomized to receive a single dose of intravenous 25 mg/kg caffeine citrate or saline placebo. The primary efficacy outcome was a 24-hour apnea-free period beginning after completion of the blinded study drug infusion. Secondary outcomes were frequency of apnea by 24, 48, and 72 hours after study medication, need for noninvasive/invasive ventilation, and length of stay in the hospital's pediatric intensive care/step-down unit. RESULTS:A total of 90 infants diagnosed with viral bronchiolitis associated with apnea (median age, 38 days) were enrolled. The rate of respiratory virus panel positivity was similar in the 2 groups (78% for the placebo group vs 84% for the caffeine group). The geometric mean duration to a 24-hour apnea-free period was 28.1 hours (95% CI, 25.6-32.3 hours) for the caffeine group and 29.1 hours (95% CI, 25.7-32.9 hours) for the placebo group (P = .88; OR, 0.99; 95% CI, 0.83-1.17). The frequency of apnea at 24 hours, 24-48 hours, and 48-72 hours after enrollment and the need for noninvasive and invasive ventilation were similar in the 2 groups. No safety issues were reported. CONCLUSIONS:A single dose of caffeine citrate did not significantly reduce apnea episodes associated with bronchiolitis. TRIAL REGISTRATION:Clinicaltrials.gov: NCT01435486.
| S-EPMC7126124 | biostudies-literature
Project description:BackgroundGroup patient visits are medical appointments shared among patients with a common medical condition. This care delivery method has demonstrated benefits for individuals with chronic conditions but has not been evaluated for Parkinson disease (PD).MethodsWe conducted a 12-month, randomized trial of group patient visits vs usual (one-on-one) care for patients with PD. Visits were led by one of 3 study physicians, included patients and caregivers, and lasted approximately 90 minutes. Those receiving group visits had 4 sessions over 12 months. The primary outcome measure was feasibility as measured by the ability to recruit participants and by the proportion of participants who completed the study. The primary efficacy outcome was quality of life as measured by the PD Questionnaire-39.ResultsThirty patients and 27 caregivers enrolled in the study. Thirteen of the 15 patients randomized to group patient visits and 14 of the 15 randomized to usual care completed the study. Quality of life measured 12 months after baseline between the 2 groups was not different (25.9 points for group patient visits vs 26.0 points for usual care; p = 0.99).ConclusionsGroup patient visits may be a feasible means of providing care to individuals with PD and may offer an alternative or complementary method of care delivery for some patients and physicians.Classification of evidenceThis study provides Class II evidence that group patient visits did not improve quality of life for individuals with PD over a 1-year period.
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Project description:BackgroundStudies suggest that dihydropyridine calcium-channel blockers may be associated with reduced risk for Parkinson disease (PD).ObjectiveTo assess the effect of isradipine, a dihydropyridine calcium-channel blocker, on the rate of clinical progression of PD.DesignMulticenter, randomized, parallel-group, double-blind, placebo-controlled trial. (ClinicalTrials.gov: NCT02168842).Setting57 Parkinson Study Group sites in North America.ParticipantsPatients with early-stage PD (duration <3 years) who were not taking dopaminergic medications at enrollment.Intervention5 mg of immediate-release isradipine twice daily or placebo for 36 months.MeasurementsThe primary outcome was change in the Unified Parkinson's Disease Rating Scale (UPDRS) parts I to III score measured in the antiparkinson medication "ON" state between baseline and 36 months. Secondary outcomes included time to initiation and use of antiparkinson medications, time to onset of motor complications, change in nonmotor disability, and quality-of-life measures.Results336 patients were randomly assigned (mean age, 62 years [SD, 9]; 68% men; disease duration, 0.9 year [SD, 0.7]; mean UPDRS part I to III score, 23.1 [SD, 8.6]); 95% of patients completed the study. Adjusted least-squares mean changes in total UPDRS score in the antiparkinson medication ON state over 36 months for isradipine and placebo recipients were 2.99 (95% CI, 0.95 to 5.03) points versus 3.26 (CI, 1.25 to 5.26) points, respectively, with a treatment effect of -0.27 (CI, -3.02 to 2.48) point (P = 0.85). Statistical adjustment for antiparkinson medication use did not change the findings. Secondary outcomes showed no effect of isradipine treatment. The most common adverse effects of isradipine were edema and dizziness.LimitationThe isradipine dose may have been insufficient to engage the target calcium channels associated with neuroprotective effects.ConclusionLong-term treatment with immediate-release isradipine did not slow the clinical progression of early-stage PD.Primary funding sourceNational Institute of Neurological Disorders and Stroke.
| S-EPMC7465126 | biostudies-literature
Project description:OBJECTIVE:To investigate the kinetics and metabolism of caffeine in serum from patients with Parkinson disease (PD) and controls using liquid chromatography-mass spectrometry. METHODS:Levels of caffeine and its 11 metabolites in serum from 108 patients with PD and 31 age-matched healthy controls were examined by liquid chromatography-mass spectrometry. Mutations in caffeine-associated genes were screened by direct sequencing. RESULTS:Serum levels of caffeine and 9 of its downstream metabolites were significantly decreased even in patients with early PD, unrelated to total caffeine intake or disease severity. No significant genetic variations in CYP1A2 or CYP2E1, encoding cytochrome P450 enzymes primarily involved in metabolizing caffeine in humans, were detected compared with controls. Likewise, caffeine concentrations in patients with PD with motor complications were significantly decreased compared with those without motor complications. No associations between disease severity and single nucleotide variants of the ADORA2A gene encoding adenosine 2A receptor were detected, implying a dissociation of receptor sensitivity changes and phenotype. The profile of serum caffeine and metabolite levels was identified as a potential diagnostic biomarker by receiver operating characteristic curve analysis. CONCLUSION:Absolute lower levels of caffeine and caffeine metabolite profiles are promising diagnostic biomarkers for early PD. This is consistent with the neuroprotective effect of caffeine previously revealed by epidemiologic and experimental studies. CLASSIFICATION OF EVIDENCE:This study provides Class III evidence that decreased serum levels of caffeine and its metabolites identify patients with PD.
| S-EPMC5791797 | biostudies-literature
Project description:To determine whether falls can be prevented with minimally supervised exercise targeting potentially remediable fall risk factors, i.e., poor balance, reduced leg muscle strength, and freezing of gait, in people with Parkinson disease.Two hundred thirty-one people with Parkinson disease were randomized into exercise or usual-care control groups. Exercises were practiced for 40 to 60 minutes, 3 times weekly for 6 months. Primary outcomes were fall rates and proportion of fallers during the intervention period. Secondary outcomes were physical (balance, mobility, freezing of gait, habitual physical activity), psychological (fear of falling, affect), and quality-of-life measures.There was no significant difference between groups in the rate of falls (incidence rate ratio [IRR] = 0.73, 95% confidence interval [CI] 0.45-1.17, p = 0.18) or proportion of fallers (p = 0.45). Preplanned subgroup analysis revealed a significant interaction for disease severity (p < 0.001). In the lower disease severity subgroup, there were fewer falls in the exercise group compared with controls (IRR = 0.31, 95% CI 0.15-0.62, p < 0.001), while in the higher disease severity subgroup, there was a trend toward more falls in the exercise group (IRR = 1.61, 95% CI 0.86-3.03, p = 0.13). Postintervention, the exercise group scored significantly (p < 0.05) better than controls on the Short Physical Performance Battery, sit-to-stand, fear of falling, affect, and quality of life, after adjusting for baseline performance.An exercise program targeting balance, leg strength, and freezing of gait did not reduce falls but improved physical and psychological health. Falls were reduced in people with milder disease but not in those with more severe Parkinson disease.This study provides Class III evidence that for patients with Parkinson disease, a minimally supervised exercise program does not reduce fall risk. This study lacked the precision to exclude a moderate reduction or modest increase in fall risk from exercise.Australian New Zealand Clinical Trials Registry (ACTRN12608000303347).
| S-EPMC4335992 | biostudies-literature
Project description:There is a paucity of therapies for gait impairment in Parkinson disease (PD). Open-label studies have suggested improved gait after treatment with methylphenidate (MPD).To evaluate the efficacy of MPD for the treatment of gait impairment in PD.Twenty-seven subjects with PD and moderate gait impairment were screened for this 6-month placebo-controlled, double-blind study. Subjects were randomly assigned to MPD (maximum, up to 80 mg/day) or placebo for 12 weeks and crossed over after a 3-week washout. The primary outcome measure was change in a gait composite score (stride length + velocity) between groups at 4 and 12 weeks. Secondary outcome measures included changes in motor function, as measured by the Unified Parkinson's Disease Rating Scale (UPDRS), Freezing of Gait Questionnaire (FOGQ), number of gait-diary freezing episodes, and measures of depression, sleepiness, and quality of life. Three-factor repeated-measures analysis of variance was used to measure changes between groups.Twenty-three eligible subjects with PD were randomized and 17 completed the trial. There was no change in the gait composite score or treatment or time effect for any of the variables. Treatment effect was not modified by state or study visit. Although there was a trend for reduced frequency of freezing and shuffling per diary, the FOGQ and UPDRS scores worsened in the MPD group compared to placebo. There was a marginal improvement in some measures of depression.MPD did not improve gait and tended to worsen measures of motor function, sleepiness, and quality of life.This study provides Class III evidence for the lack of benefit of MPD on PD-associated gait impairment.NCT00526630.
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