Early and intensive motor training to enhance neurological recovery in people with spinal cord injury: trial protocol.

STUDY DESIGN: Protocol for a multi-centre randomised controlled trial (the SCI-MT trial). OBJECTIVES: To determine whether 10 weeks of intensive motor training enhances neurological recovery in people with recent spinal cord injury (SCI). SETTING: Fifteen spinal injury units in Australia, Scotland, England, Italy, Netherlands, Norway, and Belgium. METHODS: A pragmatic randomised controlled trial will be undertaken. Two hundred and twenty people with recent SCI (onset in the preceding 10 weeks, American Spinal Injuries Association Impairment Scale (AIS) A lesion with motor function more than three levels below the motor level on one or both sides, or an AIS C or D lesion) will be randomised to receive either usual care plus intensive motor training (12 h of motor training per week for 10 weeks) or usual care alone. The primary outcome is neurological recovery at 10 weeks, measured with the Total Motor Score from the International Standards for Neurological Classification of SCI. Secondary outcomes include global measures of motor function, ability to walk, quality of life, participants' perceptions about ability to perform self-selected goals, length of hospital stay and participants' impressions of therapeutic benefit at 10 weeks and 6 months. A cost-effectiveness study and process evaluation will be run alongside the trial. The first participant was randomised in June 2021 and the trial is due for completion in 2025. CONCLUSIONS: The findings of the SCI-MT Trial will guide recommendations about the type and dose of inpatient therapy that optimises neurological recovery in people with SCI. TRIAL REGISTRATION: ACTRN12621000091808 (1.2.2021).

Intravesical hyaluronic acid with chondroitin sulphate to prevent urinary tract infection after spinal cord injury.

CONTEXT/OBJECTIVE: Prevention of urinary tract infection (UTI) after spinal cord injury is an important goal. Intravesical hyaluronic acid with chondroitin sulphate (HA+CS) has been effective in preventing UTI in other settings. We aimed to demonstrate safety and feasibility of a standard treatment course of 7 intravesical HA+CS instillations over 12 weeks, in patients with acute (Arm A) and chronic (Arm B) spinal cord injury (SCI). DESIGN: Follow-up of adverse events, quality of life bladder management difficulty (BMD) and bladder complication (BC) T-scores at baseline (Arm B only), 12 and 24 weeks, and symptomatic urinary tract infection (UTI). RESULTS: Of 33 and 14 individuals screened, 2 and 8 participants were recruited to the study for Arm A and Arm B respectively. Of the 10 participants, 8 completed all 7 instillations. HA+CS commonly caused cloudy urine with urinary sediment which was mild and short-lived. In Arm B, a mean reduction in BMD and BC T-scores was observed from baseline (57.3 and 54.4 respectively), of 6.8 and 4.3 at 12 weeks and 1.6 and 2.8 at 24 weeks, respectively. Four participants with a history of frequent UTI in the prior 12 months did not have UTI in the 24 weeks of the study. CONCLUSIONS: HA+CS was well tolerated. Recruitment was more difficult in early acute SCI; participants with chronic SCI were highly motivated to reduce UTI and manage self-administration without difficulty. Larger case-control or randomized controlled trials in patients with neurogenic bladder from SCI are warranted. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03945110.

Glutamine reduces postprandial glycemia and augments the glucagon-like peptide-1 response in type 2 diabetes patients.

Impaired glucagon-like peptide (GLP-1) secretion or response may contribute to ineffective insulin release in type 2 diabetes. The conditionally essential amino acid glutamine stimulates GLP-1 secretion in vitro and in vivo. In a randomized, crossover study, we evaluated the effect of oral glutamine, with or without sitagliptin (SIT), on postprandial glycemia and GLP-1 concentration in 15 type 2 diabetes patients (glycated hemoglobin 6.5 ± 0.6%). Participants ingested a low-fat meal (5% fat) after receiving either water (control), 30 g l-glutamine (Gln-30), 15 g L-glutamine (Gln-15), 100 mg SIT, or 100 mg SIT and 15 g L-glutamine (SIT+Gln-15). Studies were conducted 1-2 wk apart. Blood was collected at baseline and postprandially for 180 min for measurement of circulating glucose, insulin, C-peptide, glucagon, and total and active GLP-1. Gln-30 and SIT+Gln-15 reduced the early (t = 0-60 min) postprandial glycemic response compared with control. All Gln treatments enhanced the postprandial insulin response from t = 60-180 min but had no effect on the C-peptide response compared with control. The postprandial glucagon concentration was increased by Gln-30 and Gln-15 compared with control, but the insulin:glucagon ratio was not affected by any treatment. In contrast to Gln-30, which tended to increase the total GLP-1 AUC, SIT tended to decrease the total GLP-1 AUC relative to control (both P = 0.03). Gln-30 and SIT increased the active GLP-1 AUC compared with control (P = 0.008 and P = 0.01, respectively). In summary, Gln-30 decreased the early postprandial glucose response, enhanced late postprandial insulinemia, and augmented postprandial active GLP-1 responses compared with control. These findings suggest that glutamine may be a novel agent for stimulating GLP-1 concentration and limiting postprandial glycemia in type 2 diabetes.