Protocol for thiamine and folic acid in the treatment of cognitive impairment in maintenance haemodialysis patients: a prospective, randomised, placebo-controlled, double-blind, multicentre study

IntroductionCognitive impairment (CI) is the common complications in maintenance haemodialysis (MHD) patients. Recently, the pathogenesis of CI has been discussed and oxidative stress is one of the main mechanisms in these patients. Thiamine and folic acid, which play an important role in relieving the production of reactive oxygen species, reducing homocysteine levels, improving oxidative stress in the nervous system. In pilot study, cognitive function was significantly improved in the group with thiamine and folic supplementation. Based on this result, we hypothesise that thiamine combined with folic acid supplementation may improve cognitive function in patients with MHD.Methods and analysisIn this prospective, randomised, placebo-controlled, double-blind, multicentre study, we will enrol patients undergoing haemodialysis who has the Montreal Cognitive Assessment score lower than 26 to treatment group (thiamine 90 mg/day combined with folic acid 30 mg/day) or control group (thiamine placebo 90 mg/day combined with folic acid placebo 30 mg/day). All subjects will be followed up for 96 weeks. The primary endpoint is the comparison of Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) score between treatment group and control group at 96 weeks of follow-up. The secondary endpoints include serum thiamine, folate, homocysteine levels, cranial functional MRI and survival. The central randomisation method will be adopted and the principles of placebo-controlled, double-blind randomised control will be followed. The comparisons among ADAS-Cog scores and other secondary endpoints over time within subjects is conducted by using repeated measure analysis of variance (ANOVA) or generalised estimating equations (GEE). Pairwise t-test with Bonferroni adjustment is performed for multiple comparisons. On the other hand, for comparisons between treatment and control group, simple one-way ANOVA, GEE or Wilcoxon rank sum test is used. The χ2 method is used for statistical analysis of the categorical data. Kaplan-Meier survival curve is used for survival analysis. A p<0.05 is considered statistically significant difference.Ethics and disseminationThis trial has been approved by Shanghai Jiao Tong University School of Medicine, Renji Hospital Ethics Committee (KY2019-199). After publication of study results, trial report will be published in peer-reviewed journals and/or in national or international conferences.Trial registration numberChiCTR2000029297.

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INTERVENTION EFFECT OF FOLIC ACID AND VITAMIN B12 ON VASCULAR COGNITIVE IMPAIRMENT COMPLICATED WITH HYPERHOMOCYSTEINEMIA / EFEKAT INTERVENCIJE FOLNOM KISELINOM I VITAMINOM B12 NA VASKULARNI KOGNITIVNI POREMEĆAJ KOMPLIKOVAN HIPERHOMOCISTEINEMIJOM

Journal of Medical Biochemistry ◽

10.2478/jomb-2013-0033 ◽

2013 ◽

Vol 33 (2) ◽

pp. 169-174 ◽

Cited By ~ 2

Author(s):

Bo Jiang ◽

Chengyun Ding ◽

Guoen Yao ◽

Cunshan Yao ◽

Yunyan Zhang ◽

...

Keyword(s):

Cognitive Impairment ◽

Folic Acid ◽

Cognitive Function ◽

Intervention Group ◽

Vascular Cognitive Impairment ◽

Event Related Potential ◽

Control Group ◽

Before And After ◽

And Control ◽

Cognitive Impairment No Dementia

Summary Background: Hyperhomocysteinemia (HHcy) may be corre- lated with cognitive function. Although intervention with folic acid and VitB12 can decrease the homocysteine (Hey) level, its effect on cognitive function remains uncertain. This prospective study aimed to explore the effects of folic acid and VitB/!2 on the ^су an<^ cognitive function in patients with vascular cognitive impairment-no dementia (VCIND) complicated with HHcy. Methods: A total of 120 patients with VCIND complicated fcy HHcy were randomly selected. They were divided into inter- vention and control groups. The intervention group was given 5 mg of folic acid per day and 500 цд of VitB^ thrice per day apart from conventional therapy. Folic acid, V'itBl2, and Hey were determined and Montreal cognitive assess- ment (MoCA) and event-related potential P300 determination were performed before and after treatment. Results: Before treatment, no significant differences in the folic acid, VitB^, Hey, MoCA, and P300 parameters were observed between the groups. After treatment, the folic acid and VitBl2 levels increased and the Hey level decreased in the intervention group compared with that before treatment and in the control group. At 24 weeks, the MoCA score and P300 outcomes in the intervention group improved com- pared with those before treatment and in the control group. Conclusions: Folic acid and VitB^ effectively decrease the Hey level in VCIND patients and improve their cognitive functions.

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Effects of Folic Acid Combined with DHA Supplementation on Cognitive Function and Amyloid-β-Related Biomarkers in Older Adults with Mild Cognitive Impairment by a Randomized, Double Blind, Placebo-Controlled Trial

Journal of Alzheimer s Disease ◽

10.3233/jad-200997 ◽

2021 ◽

pp. 1-13

Author(s):

Dong Bai ◽

Junting Fan ◽

Mengyue Li ◽

Cuixia Dong ◽

Yiming Gao ◽

...

Keyword(s):

Cognitive Impairment ◽

Folic Acid ◽

Mild Cognitive Impairment ◽

Cognitive Function ◽

Digit Span ◽

Controlled Trial ◽

Amyloid Β ◽

Amyloid Β Peptide ◽

Double Blind ◽

Full Scale Intelligence Quotient

Background: The neuroprotective benefits of combined folic acid and docosahexaenoic acid (DHA) on cognitive function in mild cognitive impairment (MCI) patients are suggested but unconfirmed. Objective: To explore the effects of 6-month folic acid + DHA on cognitive function in patients with MCI. Methods: Our randomized controlled trial (trial number ChiCTR-IOR-16008351) was conducted in Tianjin, China. We divided 160 MCI patients aged > 60 years into four regimen groups randomly: folic acid (0.8 mg/day) + DHA (800 mg/day), folic acid (0.8 mg/day), DHA (800 mg/day), and placebo, for 6 months. Cognitive function and blood amyloid-β peptide (Aβ) biomarker levels were measured at baseline and 6 months. Cognitive function was also measured at 12 months. Results: A total of 138 patients completed this trial. Folic acid improved the full-scale intelligence quotient (FSIQ), arithmetic, and picture complement scores; DHA improved the FSIQ, information, arithmetic, and digit span scores; folic acid + DHA improved the arithmetic (difference 1.67, 95% CI 1.02 to 2.31) and digital span (1.33, 0.24 to 2.43) scores compared to placebo. At 12 months, all scores declined in the intervention groups. Folic acid and folic acid + DHA increased blood folate (folic acid + DHA: 7.70, 3.81 to 11.59) and S-adenosylmethionine (23.93, 1.86 to 46.00) levels and reduced homocysteine levels (–6.51, –10.57 to –2.45) compared to placebo. DHA lower the Aβ40 levels (–40.57, –79.79 to –1.35) compared to placebo (p < 0.05), and folic acid + DHA reduced the Aβ42 (–95.59, –150.76 to –40.43) and Aβ40 levels (–45.75, –84.67 to –6.84) more than DHA (p < 0.05). Conclusion: Folic acid and DHA improve cognitive function and reduce blood Aβ production in MCI patients. Combination therapy may be more beneficial in reducing blood Aβ-related biomarkers.

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Ganji Formulation for Patients with Hepatocellular Carcinoma Who Have Undergone Surgery: A Multicenter, Randomized, Double-Blind, Controlled Trial

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/9492034 ◽

2019 ◽

Vol 2019 ◽

pp. 1-6

Author(s):

Jing-Hao Zhang ◽

Chao Zheng ◽

Xiao-Jun Zhu ◽

Xin Zhang ◽

Zhi-Jun Hou ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Treatment Group ◽

Liver Resection ◽

Controlled Trial ◽

Disease Free Survival ◽

Control Group ◽

Double Blind ◽

Local Ablation ◽

Significant Difference ◽

And Control

Objective. To ascertain the efficacy and safety of Ganji Formulation (GF) for patients with Hepatocellular carcinoma (HCC) who had undergone surgery. Materials and Methods. A total of 262 HCC patients who had undergone liver resection, local ablation, or transcatheter arterial chemoembolization (TACE) were divided randomly into the treatment group and control group. The former was treated with GF and the later with placebo, both for 6 months. The primary endpoint was overall survival (OS). Second endpoints were disease-free survival (DFS) or time to disease progression (TTP). Results. OS of the treatment group was significantly longer than that of the control group (P < 0.05). Subgroup analysis showed that, for patients who received TACE, the TTP was significantly longer in the treatment group than in the control group (P < 0.05). However, for patients who underwent liver resection or local ablation, there was no significant difference in DFS between the two groups (P > 0.05). Conclusion. GF could improve postoperative cumulative survival and prolong the TTP. This clinical trial number is registered with ChiCTR-IOR-15007349.

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Intravenous methylcobalamin effectively ameliorated painful diabetic neuropathy: A randomized double-blind placebo controlled trial

Romanian Journal of Neurology ◽

10.37897/rjn.2021.3.12 ◽

2021 ◽

Vol 20 (3) ◽

pp. 335-341

Author(s):

Thomas Eko Purwata ◽

◽

I Putu Eka Widyadharma ◽

Made Rudy ◽

Andreas Soejitno ◽

...

Keyword(s):

Treatment Group ◽

Diabetic Neuropathy ◽

Rating Scale ◽

Controlled Trial ◽

Control Group ◽

Painful Diabetic Neuropathy ◽

Double Blind ◽

Entire Study ◽

Double Blind Placebo ◽

And Control

Objective. Painful diabetic neuropathy (PDN) is a prevalent debilitating consequence of diabetes mellitus with lack of satisfactory therapeutic options. Methylcobalamin (MeCbl) is one of vitamin B12 analogs with known neurotrophic effects. We aimed to determine if MeCbl can relieve PDN. Materials and methods. This was a randomized (1:1) double-blind placebo-controlled trial involving PDN patients. Treatment and control group received daily 12.5 mg oral amitriptyline bid with either 500 µg of intravenous MeCbl or saline injection given on alternating days, respectively, for a 9-consecutive day period. PDN was assessed with douleur neuropathique 4 (DN4) questionnaire. Numeric pain rating scale (NPRS) was used to monitor pain intensity and treatment response. All investigators and patients were kept blinded throughout the study period. Outcomes. 42 patients, 21 on each arm had completed the study. The NPRS reduction can already be observed as early as day 2 post-intervention. Both the treatment and control group demonstrated sustained reduction of NPRS by almost one point per each time point of evaluation in the first three days (p<0.001). NPRS reduction remained until the end of the study period. The treatment group had a significantly lower NPRS score by 1.29 than that of the control group during the entire study period (95% CI -1.84 – -0.75; p < 0.001). Treatment group experienced significantly higher NPRS reduction when compared with control (4.19±1.54 vs. 2.1± 0.83; 95% CI 1.32-2.87; p < 0.001), i.e. 62.6% from baseline. Conclusions. MeCbl significantly and safely relieved PDN in a relatively rapid onset.

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The Efficacy of Mindfulness-Based Alzheimer’s Stimulation (Mbas) in the Progression of Cognitive Impairment: A Double-Blind, Randomized Clinical Trial

European Journal of Investigation in Health, Psychology and Education ◽

10.3390/ejihpe4020009 ◽

2014 ◽

Vol 4 (2) ◽

pp. 101-112

Author(s):

Domingo Jesús Quintana Hernández ◽

María del Pino Quintana Montesdeoca

Keyword(s):

Clinical Trial ◽

Cognitive Impairment ◽

Randomized Clinical Trial ◽

Repeated Measures ◽

Cognitive Stimulation ◽

Mindfulness Practice ◽

Controlled Study ◽

Control Group ◽

Double Blind ◽

And Control

We conducted a randomized, controlled study in order to investigate the feasibility, security as well as the effects of the practice of mindfulness upon the evolution of AD. The efficacy of a Mindfulness-based Cognitive Stimulation program for Alzheimer’s patients was tested in this double-blind, randomized clinical trial, using repeated measures of CAMDEX (CAMCOG y MMSE) every six months during two years. A total of 168 patients, presenting a Probable Alzheimer Disease according to NINCDS-ADRDA criteria and treated with donepezil, were randomly assigned to the four following non-pharmacological treatments: standard cognitive stimulation, progressive muscular relaxation, mindfulness-based Alzheimer stimulation and control group, which received no intervention. Each experimental group worked in 90-minute sessions, three times per week during two years (a total of 96 weeks). Results indicated that the Mindfulness-based Alzheimer Stimulation group did not show as much a significant decline of cognitive function as the other groups did. Therefore, it seems that mindfulness practice, as implemented in this program, can have a preventive role against the progression of cognitive impairment in AD. These results support the use of mindfulness as a non-pharmacological treatment.

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A randomized, double-blind, parallel-group, placebo-controlled, multicenter, phase II clinical study of famitinib in the treatment of advanced metastatic colorectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.3_suppl.513 ◽

2015 ◽

Vol 33 (3_suppl) ◽

pp. 513-513 ◽

Cited By ~ 8

Author(s):

Rui-hua Xu ◽

Lin Shen ◽

Keming Wang ◽

Gang Wu ◽

Chunmei Shi ◽

...

Keyword(s):

Colorectal Cancer ◽

Clinical Study ◽

Treatment Group ◽

Adverse Events ◽

Phase Ii ◽

Advanced Colorectal Cancer ◽

Control Group ◽

Double Blind ◽

Phase Ii Clinical Study ◽

And Control

513 Background: Colorectal cancer (CRC) is the third most frequently diagnosed cancer and is the fifth leading cause of cancer death in China. No standard care is available for patients with advanced CRC who failed the second-line treatment. Famitinib is a small-molecular, multi-target receptor tyrosine kinase inhibitor which primarily acts against angiogenesis. This phase II study was designed to evaluate the efficacy and safety of famitinib in the treatment of advanced colorectal cancer. Methods: This is a multi-center, randomized, double-blind, placebo-controlled, phase II clinical study (ClinicalTrials.gov Registration No.: NCT01762293). Totally 154 patients with advanced colorectal cancer who failed second or later-line treatments were randomized in a 2:1 ratio to receive either famitinib or placebo at 25 mg each day in each treatment cycle. The primary endpoint was progression-free survival (PFS), and the secondary endpoints include overall survival (OS), objective response rate (ORR), disease control rate (DCR), quality of life (QoL) and safety. The statistical analyses of endpoints were using intent-to-treat population. Results: Of 154 patients randomized, the mPFS was 2.8 and 1.5 months in the treatment group and control group, respectively (p=0.0034; HR=0.58). The ORR was 2.02% and 0.00% (p=0.54) and the DCR was 57.58% and 30.91% (p=0.0023) in the treatment group and control group, respectively. Analysis of OS data is ongoing. The frequently reported adverse events (AEs) include neutropenia, thrombocytopenia, hypertension, proteinuria, and hand-foot syndrome and were most grade 1/2. The incidences of serious adverse events (SAEs) for the famitinib and placebo groups were 11.11% and 9.09%, respectively (p=0.7884). Overall, famitinib was well tolerated and toxicities were manageable. Conclusions: Famitinib improved the PFS in patients with advanced metastatic colorectal cancer resulting in higher ORR and DCR in the treatment group with good safety and tolerability. Clinical trial information: NCT01762293.

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Effect of Pushen capsule for treating vascular mild cognitive impairment: a pilot observational study

Journal of International Medical Research ◽

10.1177/0300060519859766 ◽

2019 ◽

Vol 47 (11) ◽

pp. 5483-5496 ◽

Cited By ~ 1

Author(s):

Shuo Li ◽

Geyin Cao ◽

Qiwen Deng ◽

Dan Zhu ◽

Fuling Yan

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Cognitive Function ◽

Treatment Group ◽

Ginkgo Biloba ◽

Rating Scale ◽

Memory Loss ◽

Control Treatment ◽

Control Group ◽

Subjective Memory

Objective Traditional Chinese medicine (TCM) may be beneficial for vascular dementia (VaD). We evaluated the efficacy of Pushen capsule, a compound containing several TCM components, for treating vascular mild cognitive impairment (VaMCI). Methods Seventy outpatients with VaMCI were randomized to Pushen capsule or control treatment with Ginkgo biloba. Mini Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Subjective Memory Loss Rating Scale scores; and lipid, lipoprotein, and haemorheological parameters were collected at baseline, week 4, and week 12 of treatment. Results MMSE score at week 12 was significantly higher in the treatment group compared with baseline ( t = −2.352) but was not significantly different from week 12 in the control group. The MoCA score at week 12 was higher than that at baseline for both the treatment and control groups ( t = −2.619 and −2.582, respectively), as was the “delayed recall” item score. Subjective memory loss score and the cognitive function “forgetting acquaintance's name” were significantly higher in the treatment group at week 12 than at baseline ( t = −2.621 and χ2 = 4.419, respectively). Lipid, lipoprotein, and haemorheological parameters were significantly different after treatment in both groups. Conclusion The benefits of Pushen capsule on cognitive function in VaMCI were comparable with that of Ginkgo biloba.

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Pengaruh kombinasi vitamin c dan vitamin e terhadap Kadar malondialdehid plasma pasien diabetes mellitus tipe 2

JURNAL GIZI INDONESIA ◽

10.14710/jgi.4.1.1-8 ◽

2016 ◽

Vol 4 (1) ◽

pp. 1-8

Author(s):

Yade Kurnia Yasin ◽

Martha Irene Kartasurya ◽

RA Kisdjamiatun RMD

Keyword(s):

Oxidative Stress ◽

Diabetes Mellitus ◽

Vitamin E ◽

Treatment Group ◽

Vitamin C ◽

Fasting Blood Glucose ◽

Control Group ◽

Double Blind ◽

Control Group Design ◽

Before And After

Background: Malondialdehyde (MDA) levels produced by oxidative stress in type 2 diabetes mellitus (T2DM) is higher than in non diabetes patients. Vitamin C and E inhibit oxidative stress and MDA production. The purpose of this study was to prove the effects of combined vitamin C and vitamin E on MDA plasma levels in T2DM patients.Methods: This double blind randomized pre post test control group design was carried out on 35 patients with T2DM without complication (age 40-60 yr) in Makassar. The treatment group (n=18) received vitamin C 250 mg/day plus vitamin E 400 IU/day and the control group (n=17) received placebo (seaweed powder 250 mg), for six weeks. Vitamin C was consumed before meal and vitamin E after meal. MDA levels were measured before and after supplementation by using TBARs method. Food intake and activity were derived from 24-hour recall method.Results: There was no different on MDA levels at baseline (p=0.151). At the end of the study, MDA levels increased in control group (5.8±2.74 to 7.2±3.00 nmol/ml; p=0.044) but not in the treatment group (7.2±2.88 to 7.7±2.02 nmol/ml; p=0.490). There was no difference in MDA alteration between the goups (p=0.316). There was no different in MDA levels at the end of the study (p=0.061) and confirmed after controlling the confounding variables: vitamin E intake and fasting blood glucose (p=0.809). Conclusion: Combined vitamin C 250 mg and vitamin E 400 IU for 6 weeks did not reduce MDA levels, but inhibit MDA production in T2DM patients.

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Efek suplementasi kombinasi zat besi, vitamin C, dan asam folat terhadap peningkatan kadar hemoglobin dan kapasitas VO2 maks pada atlet sepak bola divisi utama dan satu nasional di Daerah Istimewa Yogyakarta

Jurnal Gizi Klinik Indonesia ◽

10.22146/ijcn.17490 ◽

2006 ◽

Vol 3 (2) ◽

pp. 71

Author(s):

Zainal Abidin ◽

Woro Woro ◽

Mochammad Noerhadi

Keyword(s):

Folic Acid ◽

Treatment Group ◽

Vitamin C ◽

Controlled Trial ◽

Control Group ◽

Football Players ◽

Vo2 Max ◽

Significant Difference ◽

Combined Supplementation ◽

And Control

Background: Excessive endurance exercise of football players may break their blood cells and decrease the level of haemoglobin (Hb). These will influence the aerobic capacity (VO2 max) and make the need for iron (Fe) of an athlete more than that of common people.Objective: To know the influence of Fe, vitamin C (ascorbic acid), and folic acid combined supplementation to the increase of VO2 max capacity of the national main and first division club football players in Daerah Istimewa Yogyakarta.Method: The study was RCT (Randomized Controlled Trial) experimental with a completely randomized design plan. The subjects were football players of Perserikatan Sepak Bola Indonesia Mataram (PSIM), Perserikatan Sepak Bola Sleman (PSS), and Perserikatan Sepak Bola Bantul (PERSIBA). They were then divided into two groups: treatment group and control group, each of them consisted of 35 players. Treatment group were given combined supplement capsules of 100 mg Fe, 100 mg vitamin C, and 2 mg folic acid three times a week for eight weeks, while the control group were given the placebo capsules. Before and after supplementation, their Hb and VO2 max were measured. However, the physical exercises were done based on the schedule, programmed by the clubs.Results: Combined supplementation of Fe, vitamin C, and folic acid could increase Hb level significantly (p=0.008), but there was no significant difference of VO2 max capacity between treatment group and control group (p=0.062). However, there was significant correlation between the increase of Hb level and VO max capacity (r=0.712; p<0.001).Conclusion: Combined supplementation of Fe, vitamin C, and folic acid led to the increase of Hb level of main and first division clubs football players in Daerah Istimewa Yogyakarta, but could not influence their VO2 max capacity.

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