Low-dose memantine attenuated methadone dose in opioid-dependent patients: a 12-week double-blind randomized controlled trial.
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ABSTRACT:
SUBMITTER: Lee SY
PROVIDER: S-EPMC4650802 | biostudies-other | 2015
REPOSITORIES: biostudies-other
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Project description:BACKGROUND:The aim of this study is to determine whether adding combination of agents with anti-inflammatory and neurotrophic effects is more efficacious than mood stabilizer alone in improving clinical symptoms, plasma brain-derived neurotrophic factor (BDNF), cytokine levels, and metabolic profiles in patients with bipolar spectrum disorder. METHODS:In a randomized, double-blind, controlled 12-week clinical trial, patients with moderate mood symptoms (HDRS ≥ 18 or YMRS ≥ 14) were recruited. The patients were randomly assigned to a group while still undergoing regular valproate (VPA) treatments: VPA + dextromethorphan (DM) (30 mg/day) + memantine (MM) (5 mg/day) (DM30 + MM5) (n = 66), VPA + DM (30 mg/day) (DM30) (n = 69), VPA + MM (5 mg/day) (MM5) (n = 66), or VPA + Placebo (Placebo) (n = 69). Symptom severity, immunological parameters [plasma tumor necrosis factor (TNF)-α and C-reactive protein (CRP)] and plasma brain-derived neurotrophic factor (BDNF) were regularly examined. Metabolic profiles [cholesterol, triglycerides, glycosylated hemoglobin (HbA1C), fasting serum glucose, body mass index (BMI)] were measured at baseline and at 2, 8, and 12 weeks. RESULTS:Depression scores were significantly (P = 0.03) decreases and BDNF levels significantly (P = 0.04) increased in the DM30 + MM5 group than in the Placebo group. However, neither depressive scores nor BDNF levels were significantly different between the DM30, MM5, and Placebo groups. Changes in certain plasma cytokine and BDNF levels were significantly correlated with metabolic parameters. CONCLUSION:We concluded that add-on DM30 + MM5 was significantly more effective than placebo for clinical symptoms and plasma BDNF levels. Additional studies with larger samples and mechanistic studies are necessary to confirm our findings. Trial registration NCT03039842 (https://register.clinicaltrials.gov/). Trial date was from 1 Jan 2013 to 31 December 2016 in National Cheng Kung University Hospital. Registered 28 February 1 2017-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03039842?term=NCT03039842&rank=1.
| S-EPMC7049537 | biostudies-literature
Project description:ObjectivesLinaclotide is a guanylate cyclase-C agonist approved in the United States, Canada, and Mexico at a once-daily 145-μg dose for the treatment of chronic idiopathic constipation (CIC); a once-daily 72-μg dose for CIC recently received FDA approval. The trial objective was to evaluate the efficacy and safety of a 72-μg linaclotide dose in CIC patients.MethodsThis double-blind, placebo-controlled trial randomized patients with CIC (Rome III criteria) to once-daily linaclotide 72 μg or 145 μg, or placebo for 12 weeks. The primary endpoint, 12-week complete spontaneous bowel movement (CSBM) overall responder, required patients to have ≥3 CSBMs and an increase of ≥1 CSBM per week from baseline in the same week for ≥9 of 12 weeks of the treatment period. Secondary endpoints included 12-week change from baseline in bowel (SBM and CSBM frequency, stool consistency, straining) and abdominal (bloating, discomfort) symptoms, monthly CSBM responders, and 12-week CSBM responders among patients who averaged >1 SBM/week at baseline. Sustained response (12-week CSBM overall responders who met weekly criteria for 3 of the 4 final weeks (weeks 9-12) of treatment) was evaluated as an additional endpoint. Adverse events (AEs) were monitored.ResultsThe intent-to-treat population included 1,223 patients (mean age=46 years, female=77%, white=71%). The primary endpoint was met by 13.4% of linaclotide 72-μg patients vs. 4.7% of placebo patients (P<0.0001, odds ratio=3.0; statistically significant controlling for multiplicity). Sustained response was achieved by 12.4% of linaclotide 72-μg patients vs. 4.2% of placebo patients (nominal P<0.0001). Linaclotide 72-μg patients met 9-of-10 secondary endpoints vs. placebo (P<0.05; abdominal discomfort, P=0.1028). Patients treated with linaclotide 145 μg also improved CIC symptoms for the primary (12.4%) and sustained responder endpoint parameters (11.4%) and for all 10 of the secondary endpoint parameters including abdominal discomfort (P<0.05). Diarrhea, the most common AE, was mild in most instances and resulted in discontinuation of 0, 2.4%, and 3.2% of patients in the placebo, linaclotide 72-μg, and linaclotide 145-μg groups, respectively.ConclusionsOnce-daily linaclotide 72 μg significantly improved CIC symptoms in both men and women with a low rate of discontinuation due to diarrhea over 12 weeks of treatment.
| S-EPMC5770595 | biostudies-literature
Project description:Preclinical data suggests that memantine, a noncompetitive glutamate N-methyl- D-aspartate-receptor blocker used for the treatment of moderate to severe Alzheimer's disease, could reduce depressive and amotivated behavior occurring in the context of psychosocial stress. Therefore, we examined whether memantine could reduce depressive symptoms and amotivation manifesting in older adults after a disabling medical event, thereby improving their functional recovery.We recruited subjects aged 60 years and older who had recently suffered a disabling medical event and were admitted to a skilled nursing facility for rehabilitation. Participants with significant depressive symptoms, defined as a Hamilton Rating Scale for Depression score of 10 or greater, and/or significant apathy symptoms, defined as an Apathy Evaluation Scale score of 40 or greater, were randomized to memantine (10?mg/d for 1?week, then 10?mg twice daily) or placebo, for 12?weeks. We also recruited participants without depressive or apathy symptoms for naturalistic follow-up as a non-depressed comparison group. Depressive and apathy symptoms were main outcomes; functional recovery, and self-report rating of helplessness, and onset of new depressive disorders were secondary outcomes.Thirty-five older adults with significant depressive and/or apathy symptoms were randomized, of whom 27 (77.1%) completed the 12?week randomized controlled trial. Both groups showed reduction in depressive symptoms (but no significant reduction in apathy symptoms) and improved function. However, there were no group differences between the memantine-randomized and placebo randomized participants on any outcome.Memantine was not associated with superior affective or functional outcome compared with placebo in medically rehabilitating older adults with depressive and apathy symptoms.
| S-EPMC3601891 | biostudies-literature
Project description:To examine the efficacy, safety, and tolerability of vilazodone for subjects (aged 18-75 years) with generalized social anxiety disorder. Forty-four subjects with generalized social anxiety disorder (DSM-IV-TR criteria) were randomized to vilazodone or placebo in a 12-week double-blind, flexible-dose trial. Change from baseline to endpoint on the Liebowitz Social Anxiety Scale (LSAS) was the primary outcome measure. Secondary outcome measures included response and remission rates and changes in depression and anxiety. Data were collected between November 2012 and April 2014. The study was conducted at a private clinical trials facility in New York, New York. The mean baseline LSAS score was 91.9 (SD = 17.5) and the mean Clinical Global Impressions-Severity scale score was 5.3 (SD = 0.56), indicating marked to severe illness. There were no significant baseline differences in severity of social anxiety between the treatment groups. At the end of treatment, in the intent-to-treat sample (n = 39), the vilazodone group had improved significantly more than the placebo group by 14.3 points on the LSAS (t = 1.80, P = .04, one-tail test) (Cohen d = 0.58). The findings suggest that vilazodone may be a promising treatment for social anxiety disorder. Further study is needed given the limited sample size. ClinicalTrials.gov identifier: NCT01712321.
| S-EPMC4805415 | biostudies-literature
Project description:Background: Fragile X syndrome (FXS), the most common single-gene cause of intellectual disability and autism spectrum disorder (ASD), is caused by a >200-trinucleotide repeat expansion in the 5' untranslated region of the fragile X mental retardation 1 (FMR1) gene. Individuals with FXS can present with a range of neurobehavioral impairments including, but not limited to: cognitive, language, and adaptive deficits; ASD; anxiety; social withdrawal and avoidance; and aggression. Decreased expression of the γ-aminobutyric acid type A (GABAA) receptor δ subunit and deficient GABAergic tonic inhibition could be associated with symptoms of FXS. Gaboxadol (OV101) is a δ-subunit-selective, extrasynaptic GABAA receptor agonist that enhances GABAergic tonic inhibition, providing the rationale for assessment of OV101 as a potential targeted treatment of FXS. No drug is approved in the United States for the treatment of FXS. Methods: This 12-weeks, randomized (1:1:1), double-blind, parallel-group, phase 2a study was designed to assess the safety, tolerability, efficacy, and optimal daily dose of OV101 5 mg [once (QD), twice (BID), or three-times daily (TID)] when administered for 12 weeks to adolescent and adult men with FXS. Safety was the primary study objective, with key assessments including treatment-emergent adverse events (TEAEs), treatment-related adverse events leading to study discontinuation, and serious adverse events (SAEs). The secondary study objective was to evaluate the effect of OV101 on a variety of problem behaviors. Results: A total of 23 participants with FXS (13 adolescents, 10 adults) with moderate-to-severe neurobehavioral phenotypes (Full Scale Intelligence Quotient, 41.5 ± 3.29; ASD, 82.6%) were randomized to OV101 5 mg QD (n = 8), 5 mg BID (n = 8), or 5 mg TID (n = 7) for 12 weeks. OV101 was well tolerated across all 3 treatment regimens. The most common TEAEs were upper respiratory tract infection (n = 4), headache (n = 3), diarrhea (n = 2), and irritability (n = 2). No SAEs were reported. Improvements from baseline to end-of-treatment were observed on several efficacy endpoints, and 60% of participants were identified as treatment responders based on Clinical Global Impressions-Improvement. Conclusions: Overall, OV101 was safe and well tolerated. Efficacy results demonstrate an initial signal for OV101 in individuals with FXS. These results need to be confirmed in a larger, randomized, placebo-controlled study with optimal outcomes and in the most appropriate age group. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03697161.
| S-EPMC8531725 | biostudies-literature
Project description:Daily oral intake of 40 μg Aloe sterol was shown in a double-blind clinical trial to significantly increase skin barrier function, moisture and elasticity. Ultrasonographic results also suggested that the intake of Aloe sterol increases collagen content in the dermis. Here, we evaluate the effects of a much smaller dose of Aloe sterol, approximately half that used previously, on skin functions in more detail. This is a monocentric, double-blind, randomized, placebo-controlled, supplementation study of the effects of low-dose Aloe sterol on skin transepidermal water loss, hydration, collagen score, evaluation of objective or subjective symptoms, and safety after 12 weeks of daily intake. We randomly administrated either Aloe sterol or placebo to 122 healthy volunteers. Transepidermal water loss was significantly reduced and collagen score was increased in the Aloe sterol group compared with the placebo group at week 12. In the Aloe sterol group, there was significant improvement of objective skin condition (face erythema and pruritus of inner and outer arms) at week 12 compared with week 0, but not in the placebo group. Subjectively, there was significant improvement of visual analog scale of skin acne, fingernail brittleness and constipation in the Aloe sterol group. According to subgroup analysis, although not planned before the study initiation, subjects with dry skin in the Aloe sterol group had significantly increased skin hydration values at week 12 compared with the placebo group. Our results confirmed that even low-dose Aloe sterol ingestion improves skin moisture by promoting skin barrier function and dermal collagen production, which contributes to maintenance of healthy skin.
| S-EPMC7496846 | biostudies-literature
Project description:Hyperglucagonemia contributes to hyperglycemia in patients with type 1 diabetes (T1D); however, novel therapeutics that block glucagon action could improve glycemic control. This phase 2 study evaluated the safety and efficacy of volagidemab, an antagonistic monoclonal glucagon receptor (GCGR) antibody, as an adjunct to insulin therapy in adults with T1D. The primary endpoint was change in daily insulin use at week 12. Secondary endpoints included changes in hemoglobin A1c (HbA1c) at week 13, in average daily blood glucose concentration and time within target range as assessed by continuous blood glucose monitoring (CGM) and seven-point glucose profile at week 12, incidence of hypoglycemic events, the proportion of subjects who achieve HbA1c reduction of ≥0.4%, volagidemab drug concentrations and incidence of anti-drug antibodies. Eligible participants (n = 79) were randomized to receive weekly subcutaneous injections of placebo, 35 mg volagidemab or 70 mg volagidemab. Volagidemab produced a reduction in total daily insulin use at week 12 (35 mg volagidemab: -7.59 units (U) (95% confidence interval (CI) -11.79, -3.39; P = 0.040 versus placebo); 70 mg volagidemab: -6.64 U (95% CI -10.99, -2.29; P = 0.084 versus placebo); placebo: -1.27 U (95% CI -5.4, 2.9)) without meeting the prespecified significance level (P < 0.025). At week 13, the placebo-corrected reduction in HbA1c percentage was -0.53 (95% CI -0.89 to -0.17, nominal P = 0.004) in the 35 mg volagidemab group and -0.49 (95% CI -0.85 to -0.12, nominal P = 0.010) in the 70 mg volagidemab group. No increase in hypoglycemia was observed with volagidemab therapy; however, increases in serum transaminases, low-density lipoprotein (LDL)-cholesterol and blood pressure were observed. Although the primary endpoint did not meet the prespecified significance level, we believe that the observed reduction in HbA1c and tolerable safety profile provide a rationale for further randomized studies to define the long-term efficacy and safety of volagidemab in patients with T1D.
| S-EPMC9872851 | biostudies-literature
Project description:ObjectiveTo assess the efficacy and safety of infliximab versus placebo in the treatment of patients with juvenile-onset spondyloarthritis (JoSpA).MethodsPhase III, randomized, double-blind, placebo-controlled trial of 12 weeks that included patients ≤ 18 years old with JoSpA not responding to nonsteroidal anti-inflammatory drugs, sulfasalazine, or methotrexate. Patients were randomly assigned 1:1 to the infusion of infliximab 5mg/kg or placebo; completers entered then an open-label extension (OLE) period of 42 weeks. The primary endpoint was the number of active joints. Secondary outcomes included the assessment of disease activity, tender entheses, spinal mobility, serum C-reactive protein (CRP), the Bath Ankylosing Spondylitis Disease Activity and Functional Index, and the Childhood Health Assessment Questionnaire (CHAQ).ResultsWe randomized 12 patients to infliximab and 14 to placebo. No significant differences were found between groups at baseline. At week 12, the mean number of active joints was 1.4 (SD 2.4) in the infliximab group and 4.1 (SD 3.0) in the placebo group (p = 0.0002). A repeated-measures mixed model analysis that included all endpoints in the study demonstrated sustained favourable outcomes of infliximab for active joints, tender joints, swollen joints, and tender enthesis counts, as well as for CHAQ and CRP (p < 0.01). Adverse events were more frequent in the infliximab group, including infections and infusion reactions, but none of them was serious.ConclusionInfliximab is efficacious for patients with JoSpA with an inadequate response to conventional treatment. No serious adverse events with the use of infliximab were observed.
| S-EPMC9358905 | biostudies-literature
Project description:ObjectivesCognitive impairment affects up to 80% of systemic lupus erythematosus (SLE) patients within 10 years of diagnosis. Memantine, a seronergic receptor and nicotine acetylcholine receptor antagonist, acts on the glutamatergic system through the NMDA receptor and is used to treat dementia. We investigated whether it had benefit for SLE cognitive impairment.MethodsA randomized double-blind, placebo-controlled single-center 12-week trial of memantine titrated to 20 mg/d was performed, using a 2:1 randomization ratio, in 51 SLE patients. The primary outcome measures were change in the Automated Neuropsychological Assessment Metrics throughput scores at 12 weeks.ResultsThere were no statistically significant differences between treatment groups or change from baseline in any of the Automated Neuropsychological Assessment Metrics throughput scores at 6 or 12 weeks. For the American College of Rheumatology cognitive battery, the only statistically significant findings were for the Controlled Oral Word Association Test-S words at 6 and 12 weeks. At 12 weeks, the memantine group exhibited greater improvement compared with the placebo group (3.6 ± 1.8 vs 0.5 ± 3.8 words, P = 0.03). In a subset analysis limited to patients that scored ≥1 standard deviation below normal controls at baseline, no significant differences between treatment groups were found.ConclusionsIn this first clinical trial of memantine in SLE, patients treated with memantine did not exhibit significant improvement in cognitive performance compared with the placebo group, regardless of the degree of impairment at baseline, with the exception of controlled oral word association.
| S-EPMC3153605 | biostudies-literature
Project description:BackgroundDysfunction of neuroplasticity due to N-methyl-d-aspartate (NMDA) receptor hypofunction may be a causal factor for memory and executive dysfunctioning in schizophrenia. Deregulation of NMDA transmission in the prefrontal cortex may also explain negative and positive symptoms. Clozapine augmentation with memantine targets altered NMDA receptor-mediated neurotransmission in schizophrenia and showed substantial beneficial effects on several symptom domains in a small proof-of-concept study. We evaluate effects of memantine add-on treatment to clozapine for memory and executive function, and negative and positive symptoms in schizophrenia.MethodClozapine-treated patients with refractory schizophrenia were randomly assigned to 12 weeks of double-blind adjunctive treatment with memantine (n = 26) or placebo (n = 26). Crossover occurred after a 2-week placebo wash-out period. Primary endpoints were change from baseline to 12 weeks treatment and 14 weeks to 26 weeks treatment on memory and executive function using the Cambridge Neuropsychological Test Automated Battery (CANTAB), Positive and Negative Syndrome Scale (PANSS), and Clinical Global Impression Severity Scale (CGI-S). Side effects were assessed using the Liverpool University Neuroleptic Side-Effect Rating Scale.ResultsWhen compared with placebo, memantine improved a composite memory score comprising verbal recognition memory and paired associates learning task scores on the CANTAB (effect size = 0.30) and PANSS negative subscale score (effect size = 0.29). Side effects were mild and transient.ConclusionsIn patients with clozapine-treated refractory schizophrenia, memantine addition significantly improved verbal and visual memory and negative symptoms without serious adverse effects. These results justify further investigations on long-term memantine augmentation to clozapine in treatment-resistant schizophrenia.
| S-EPMC4954262 | biostudies-literature