Pergolide therapy in Parkinson's disease: a double-blind, placebo-controlled study

A double-blind, placebo-controlled study was conducted of pergolide as an adjunctive treatment to levodopa in 17 patients with advanced Parkinson's disease. There was a significant improvement (p less than 0.05) in total disability score, in gait, and in "wearing off" and "on-off" phenomena. Pergolide is a useful drug in patients with advanced Parkinson's disease.     

Low-dose bromocriptine therapy in Parkinson's disease: double-blind, placebo-controlled study

Twenty-one de novo parkinsonian patients in stage I to III of the Hoehn and Yahr scale completed a 6-month, double-blind, placebo-controlled study. Low-dose bromocriptine (15 mg daily) was effective. Rigidity improved more than tremor or bradykinesia. Sustained satisfactory benefit was seen only in patients with mild Parkinson's disease.     

Sarizotan as a treatment for dyskinesias in Parkinson's disease: a double-blind placebo-controlled trial.

The objective of this study is to conduct a dose-finding study of sarizotan in Parkinson's disease (PD) patients with dyskinesia to identify a safe dose and to identify a sensitive dyskinesia rating measure. Sarizotan is a novel compound with full 5-HT(1A) agonist properties and additional high affinity for D(3) and D(4) receptors. An open label study documented improvements in PD patients with levodopa-induced dyskinesia. There is no precedent for study designs or outcome measures in pivotal trials of antidyskinesia therapies. The approach used here was a multicenter, randomized, placebo-controlled, double-blind, parallel study. Included were PD patients optimized to levodopa and dopaminergic drugs with moderately disabling dyskinesias present greater than or equal to 25% of the waking day. Interventions included sarizotan 2, 4, or 10 mg/day or matching placebo, given in two doses. There were two outcome measures: the primary measure was change from baseline in diary-based on time without dyskinesia; the secondary measures were change from baseline in scores on the Abnormal Involuntary Movement Scale (AIMS), the composite score of Unified Parkinson's Disease Rating Scale (UPDRS) Items 32+33 (dyskinesia duration and disability) and total UPDRS. A total of 398 subjects were randomized, with 381 included in the intention-to-treat population. No significant changes occurred on sarizotan compared to placebo on any diary-based measure of dyskinesia or the AIMS score. The composite score of UPDRS Items 32+33 was significantly improved with 2 mg/day sarizotan, with a trend at 10 mg/day. Adverse events were not significantly different in sarizotan- and placebo-treated patients, but off time significantly increased with sarizotan 10 mg/day. Sarizotan 2 mg/day is a safe agent in PD patients with dyskinesia. To test its role in abating dyskinesia, future studies should focus on this dose and will use the composite score of UPDRS Items 32+33 as the primary outcome.     

The effect of amantadine on levodopa-induced dyskinesias in Parkinson's disease: a double-blind, placebo-controlled study

We performed a double-blind, placebo-controlled, crossover study to assess the effect of amantadine versus placebo on levodopa-induced dyskinesias in Parkinson's disease. We found a 24% reduction in the total dyskinesia score after amantadine administration (p = 0.004). This improvement was achieved without any influence on the severity of "on" period parkinsonism. The results confirm that amantadine reduces levodopa dyskinesias and support the hypothesis that dyskinesias can be reduced by blockade of excitatory pathways in the basal ganglia.     

Rotigotine transdermal patch in Chinese patients with early Parkinson's disease: A randomized,double-blind,placebo-controlled pivotal study

IntroductionTwo phase3 studies (SP512; SP513) involving mostly Caucasian patients showed that rotigotine (≤8 mg/24 h) was efficacious and welltolerated in early-stage Parkinson's disease (PD). We report results from a phase 3 study (SP0914/NCT01646268) investigating rotigotine in Chinese patients with early-stage PD.MethodsPatients were randomized 1:1 to rotigotine or placebo, titrated over 1–4 weeks, maintained at optimal/maximum dose (≤8 mg/24 h) for 24 weeks. Primary efficacy variable: change in Unified Parkinson's Disease Rating Scale (UPDRS) II + III total score from Baseline to End-of-Maintenance. Secondary variables: UPDRS II + III responders (≥20% decrease in UPDRS II + III) and changes in UPDRS II (activities of daily living [ADL]) and III (motor examination) subscores.ResultsOf 247 patients randomized, 113/124 (91.1%) rotigotine- and 107/123 (87.0%) placebo-treated patients completed the study. Patients: mean (SD) age: 59.4 (10.2) years; time since PD diagnosis: 1.01 (1.22) years, 60.7% male. Rotigotine significantly improved UPDRS II + III total score (change from Baseline LSmean [95%CI] treatment difference, −4.82 [−7.18 to −2.45]; P < 0.0001). UPDRS II + III responder rates were higher with rotigotine (42.3% vs 22.3%; P = 0.0006). UPDRS II and III subscores improved with rotigotine (both subscores: P < 0.0005 vs. placebo). Most frequent adverse events (AEs): nausea (8.9% rotigotine, 3.3% placebo), dizziness (8.1%, 5.7%), pruritus (8.1%, 4.1%), somnolence (8.1%, 3.3%), erythema (6.5%, 1.6%), and vomiting (5.6%, 1.6%). Thirteen (5.3%) patients discontinued due to AEs (6 rotigotine, 7 placebo).ConclusionsRotigotine was efficacious in Chinese patients with early-stage PD, providing benefits to control of ADL and motor function. Rotigotine was generally welltolerated, with similar AEs to those observed in Caucasian patients.     

Subcutaneous apomorphine in patients with advanced Parkinson's disease: a dose-escalation study with randomized, double-blind, placebo-controlled crossover evaluation of a single dose

OBJECTIVE: To further explore the efficacy and safety of subcutaneous apomorphine (APO) in treating off episodes in APO-na?ve patients with advanced Parkinson's disease (PD). METHODS: 56 patients receiving optimized oral anti-PD medication were evaluated on separate days for response to single increasing doses of APO. Acute response to oral anti-PD medication and APO dose escalation (2-10 mg) was evaluated under unblinded conditions. At the 4 mg APO dose, placebo was randomly introduced under double-blind crossover conditions. RESULTS: Mean changes from pre-dose in Unified Parkinson's Disease Rating Scale motor scores indicated significant improvement following APO 4 mg versus placebo at 20 min (p=0.0002), 40 min (p<0.0001; maximum improvement) and 90 min (p=0.0229). Improvements showed significant dose-response at 20 min, 40 min (both p<0.0001) and 90 min (p=0.0049). Adverse events were more common with APO than placebo, and also showed significant dose-response (p<0.0001). Common adverse events associated with APO included yawning, dizziness, nausea, somnolence and dyskinesias, and were generally mild to moderate. There were no significant differences between APO and placebo in the incidence of hypotension associated with a postural change from a sitting to standing position. CONCLUSIONS: Subcutaneous APO provided rapid, effective relief of off episodes associated with advanced PD.     

Zishenpingchan granules for the treatment of Parkinson's disease:a randomized,double-blind,placebo-controlled clinical trial

Levodopa preparations remain the preferred drug for Parkinson's disease.However,long-term use of levodopa may lead to a series of motor complications.Previous studies have shown that the combination of levodopa and Zishenpingchan granules(consisting of Radix Rehmanniae preparata,Lycium barbarum,Herba Taxilli,Rhizoma Gastrodiae,Stiff Silkorm,Curcuma phaeocaulis,Radix Paeoniae Alba,Rhizoma Arisaematis,Scorpio and Centipede) can markedly improve dyskinesia and delay the progression of Parkinson's disease,with especially dramatic improvements of non-motor symptoms.However,the efficacy of this combination has not been confirmed by randomized controlled trials.The current study was approved by the Hospital Ethics Committee and was registered in the Chinese Clinical Trial Register(registration number:Chi CTR-INR-1701194).From December 2014 to December 2016,128 patients(72 males and 56 females,mean age of 65.78 ± 6.34 years) with Parkinson's disease were recruited from the Department of Neurology of Longhua Hospital and Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine in China.Patients were equally allocated into treatment and control groups.In addition to treatment with dopamine,patients in treatment and control groups were given Zishenpingchan granules or placebo,respectively,for 24 weeks.Therapeutic efficacy was assessed using the Unified Parkinson's Disease Rating Scale,on-off phenomenon,Hoehn-Yahr grade,Scales for Outcomes in Parkinson's disease–Autonomic,Parkinson's disease sleep scale,Hamilton Anxiety Scale,Hamilton Depression Scale,Mini-Mental State Examination,and the Parkinson's Disease Quality of Life Questionnaire.Artificial neural networks were used to determine weights at which to scale these parameters.Our results demonstrated that Zishenpingchan granules significantly reduced the occurrence of motor complications,and were useful for mitigating dyskinesia and non-motor symptoms of Parkinson's disease.This combination of Chinese and Western medicine has the potential to reduce levodopa dosages,and no obvious side effects were found.These findings indicate that Zishenpingchan granules can mitigate symptoms of Parkinson's disease,reduce toxic side effects of dopaminergic agents,and exert synergistic and detoxifying effects.     

Levodopa improves physical fatigue in Parkinson's disease: a double-blind, placebo-controlled, crossover study.

We quantitatively investigated the effect of carbidopa/levodopa (25/100) on physical fatigue during finger tapping and force generation in a double-blind, placebo-controlled crossover study. Parkinson's disease (PD) subjects were randomly assigned to carbidopa/levodopa or placebo for Visit 1 or 2 and participated in the following two studies: (1) Finger tapping. Twenty-five PD patients used their index fingers to strike two keys 20 cm apart on a musical instrument digital interface (MIDI) keyboard. The slopes of the regression line of dwell time and movement time were used to assess the rate of fatigue development. (2) Force generation. Twelve PD patients contracted the wrist extensors maximally to obtain a baseline maximum voluntary contraction (BMVC) force. Then they repetitively contracted the wrist extensors at 50% of the BMVC for 7 seconds and rested for 3 seconds. An interval maximum voluntary contraction (IMVC) was measured every three repetitions. Fatigue was defined as an IMVC of less than 60% of the BMVC. The slope of the regression line of IMVC was used to assess the rate of force decline. These two studies were repeated 1 hour after carbidopa/levodopa (25/100) or placebo. Subjects filled out the Multidimensional Fatigue Inventory (MFI) at the beginning of the first visit. Results showed that the slope of dwell time decreased with levodopa but not with placebo (P = 0.004). The rate of force decline also decreased with levodopa but not with placebo (P = 0.01). The subscores in the dimension of physical fatigue in the MFI did not correlate with the rate changes in dwell time or the rate changes in force decline. We concluded that (1) levodopa improves physical fatigue in finger tapping and force generation, (2) physical fatigue in Parkinson's disease is at least partially related to dopamine deficiency, and (3) the MFI measures different aspects of physical fatigue compared with those measured by finger tapping and force generation.     

Aripiprazole in the treatment of patients with borderline personality disorder: a double-blind, placebo-controlled study

OBJECTIVE: Aripiprazole is a relatively new atypical antipsychotic agent that has been successfully employed in therapy for schizophrenia and schizoaffective disorders. A few neuroleptics have been used in therapy for patients with borderline personality disorder, which is associated with severe psychopathological symptoms. Aripiprazole, however, has not yet been tested for this disorder, and the goal of this study was to determine whether aripiprazole is effective in the treatment of several domains of symptoms of borderline personality disorder. METHOD: Subjects meeting criteria for the Structured Clinical Interview for DSM-III-R Personality Disorders for borderline personality disorder (43 women and 9 men) were randomly assigned in a 1:1 ratio to 15 mg/day of aripiprazole (N=26) or placebo (N=26) for 8 weeks. Primary outcome measures were changes in scores on the symptom checklist (SCL-90-R), the Hamilton Depression Rating Scale (HAM-D), the Hamilton Anxiety Rating Scale (HAM-A), and the State-Trait Anger Expression Inventory and were assessed weekly. Side effects and self-injury were assessed with a nonvalidated questionnaire. RESULTS: According to the intent-to-treat principle, significant changes in scores on most scales of the SCL-90-R, the HAM-D, the HAM-A, and all scales of the State-Trait Anger Expression Inventory were observed in the subjects treated with aripiprazole after 8 weeks. Self-injury occurred in the groups. The reported side effects were headache, insomnia, nausea, numbness, constipation, and anxiety. CONCLUSIONS: Aripiprazole appears to be a safe and effective agent in the treatment of patients with borderline personality disorder.     

Subcutaneous octreotide in cluster headache: randomized placebo-controlled double-blind crossover study

Current practical evidence-based acute treatments of cluster headache are limited to subcutaneous and intranasal formulations of sumatriptan, and oxygen. Two small randomized, double-blind trials suggested efficacy of somatostatin in cluster headache. We sought to determine whether octreotide, a somatostatin analog, is effective in the abortive treatment of acute cluster headache. Patients with episodic and chronic cluster headache, as defined by the International Headache Society, were recruited to a double-blind placebo-controlled crossover study. Patients were instructed to treat two attacks of at least moderate pain severity, with at least a 24-hour break, using subcutaneous octreotide microg or matching placebo. The primary end point was the headache response defined as very severe, severe, or moderate pain becomes mild or nil, at 30 minutes. The primary end point was examined using a multilevel analysis approach. A total of 57 patients were recruited of whom 46 provided efficacy data on attacks treated with octreotide and 45 with placebo. The headache response rate with subcutaneous octreotide was 52%, whereas that with placebo was 36%. Modeling the treatment outcome as a binomial where response was determined by treatment, using the patient as the level 2 variable, and considering period effect, sex, and cluster headache type as other variables of interest, we found that the effect of subcutaneous octreotide 100 microg was significantly superior to placebo (p < 0.01). Subcutaneous octreotide 100 microg is effective in the acute treatment of cluster headache when compared with placebo. Nonvasconstrictor treatment of acute cluster headache is possible.     

A double-blind,placebo-controlled and longitudinal study of riluzole in early Parkinson's disease

BACKGROUND: To the extent that excitotoxicity may play a role in the pathogenesis of certain neurodegenerative disorders, antagonists of glutamate, an excitatory neurotransmitter, should exert neuroprotective effects in these disorders, including Parkinson's disease (PD). METHODS: Patients in early stages of PD, not previously treated with levodopa, were randomized to receive riluzole 50mg capsules orally, taken twice daily or a matching placebo. All subjects were evaluated at baseline (pre-treatment), at 1, 3 and 6 months (post-treatment), and following a 6-week washout. After the washout, all subjects were offered an enrollment in an open label, 1-year, extension study. The principal investigator (JJ), however, remained blinded to the original assignment during the entire study. The patients were assessed by the Unified Parkinson's Disease Rating Scale (UPDRS), Activities of Daily Living (ADL), Hoehn & Yahr (HY) stage, and Schwab and England (SE) ADL scale. The quantitative assessments included Movement Time (MT) and Reaction Time (RT). Additionally, the time to initiate dopaminergic therapy was assessed. Safety was determined at each visit by clinical history and examination, a panel of blood safety laboratory tests including complete blood count, chemistry profile, and liver function studies. RESULTS: Twenty patients with a mean age of 62+/-9.02 (range: 46-73) years and mean duration of symptoms of 18+/-9.53 (range: 6-36) months were enrolled. One patient withdrew from the study because he needed more aggressive treatment of his symptoms. Analysis of the efficacy variables showed no meaningful symptomatic effect of riluzole on UPDRS score. Likewise, there was no significant change in the median HY stage, SE ADL rating, or the MT/RT. Seventeen patients (mean age 62+/-9.26) elected to continue in the open label extension study. Although the observed deterioration in UPDRS scores seemed to be more pronounced in the placebo group than in the riluzole group, the difference did not reach statistical significance. There was no statistically significant difference in the latency between enrollment and start of symptomatic therapy when patients initially treated with riluzole were compared to those initially treated with placebo (8.3 vs 9 months). CONCLUSIONS: This pilot and extension study showed that riluzole, 100mg/day, was well tolerated in patients with early PD. No evidence of symptomatic effect of riluzole was observed. Because of the exploratory nature of the design and small size of the study, it was not possible to determine whether riluzole affected the natural history of PD. The encouraging results from our study, however, suggest that larger, longitudinal studies are warranted.     

Rotigotine may improve sleep architecture in Parkinson's disease: a double-blind,randomized, placebo-controlled polysomnographic study

Background/ObjectivesGrowing evidence demonstrates that in Parkinson's Disease (PD) sleep disturbances are frequent and difficult to treat. Since the efficacy of rotigotine on sleep is corroborated by studies lacking polysomnography (PSG), this study explores the possible rotigotine-mediated impact on PSG parameters in PD patients.MethodsThis is a randomized, double-blind, placebo-controlled, parallel-group study to determine the efficacy of rotigotine vs placebo on PSG parameters in moderately advanced PD patients. An unusual protocol was utilized, since patches were maintained from 18:00 h to awakening, minimizing the possible diurnal impact on motor symptoms. All participants underwent sleep PSG recordings, subjective sleep questionnaires (Parkinson Disease Sleep Scale [PDSS], Pittsburgh Sleep Quality Index [PSQI]), and the assessment of early-morning motor disability.ResultsWe evaluated 42 PD patients (Hoehn & Yahr stages 2 and 3) with sleep impairment randomly assigned to active branch (N =21) or placebo (N = 21). Rotigotine significantly increased sleep efficiency and reduced both wakefulness after sleep onset and sleep latency compared to placebo. Moreover, the mean change in REM sleep quantity was significantly higher in the rotigotine than placebo group. The improvement of PSG parameters corresponded to the amelioration of PDSS and PSQI scores together with the improvement of patient morning motor symptoms.ConclusionsThis study demonstrated the significant effect of rotigotine on sleep quality and continuity in PD patients by promoting sleep stability and increasing REM. The effectiveness of rotigotine on sleep may be ascribed to its pharmacokinetic/pharmacodynamic profile directly on both D1 and D2 receptors.     

Evaluation of acupuncture in the treatment of Parkinson's disease: a double-blind pilot study.

As many as 40% of patients with Parkinson's disease (PD) use some form of complementary medicine during the course of their illness, and many try acupuncture. One nonblinded study of the effects of acupuncture in PD suggested that it might be helpful for some aspects of PD. We performed a double-blind, randomized, pilot study comparing acupuncture to a control nonacupuncture procedure to determine the effects of acupuncture upon a variety of PD-associated symptoms. Fourteen patients with Stage II or III PD received acupuncture or a control nonacupuncture protocol. Before and after treatment, patients were evaluated using the Motor subscale of the Unified Parkinson's Disease Rating Scale (UPDRS), the Parkinson's Disease Questionnaire (PDQ-39), and the Geriatric Depression Scale. There were no statistically significant changes for the outcomes measured. In the patients who received acupuncture, nonsignificant trends toward improvement were noted in the Activities of Daily Living score of the PDQ-39, the PDQ-39 Summary Index(c) 2005 Movement Disorder Society.     

Fluvoxamine in the treatment of demented elderly patients: a double-blind, placebo-controlled study.

The efficacy of fluvoxamine on cognitive functioning and behavioral changes was evaluated in a double-blind, placebo-controlled study of 46 elderly demented patients. The patients had a DSM-III diagnosis of primary degenerative dementia or multi-infarct dementia and were aged greater than or equal to 65 years. Twenty-two patients were given 150 mg fluvoxamine per day and 24 received placebo tablets; 14 and 15 patients, respectively, completed 6 weeks of treatment. Within treatments, there were no significant changes in median scores on neuropsychological tests (picture recall and recognition, trail making and finger tapping) or the GBS scale scores (degrees of dementia) or GBS subscale score (clinical profiles, including symptoms common in dementia, motor, emotional and intellectual functioning). Between treatments, the median changes in psychometric test scores did not differ significantly. However, within and between treatments, there were trends favoring fluvoxamine on symptoms common in dementia (confusion, irritability, anxiety, fear-panic, mood level and restlessness). In conclusion, the study does not support the hypothesis that fluvoxamine improves cognitive functioning or behavioral changes in elderly dementia patients.