SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT03172026

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

Maraviroc to Augment Rehabilitation Outcomes After Stroke

After stroke, the combination of progressive skills practice in an adequate dose, exercise for fitness, and reduced sedentary time will augment motor and cognitive outcomes. Sensorimotor and cognitive improvements after stroke often reach a general plateau by approximately 12 weeks after onset, however. Drugs that might enhance learning or neural repair, as well as other molecular and synaptic adaptations that occur during skills training and fitness exercise, might extend that recovery curve, although to date only fluoxetine has given any hint of this. Most trials have tested agents that modulate neurotransmitters. Several very recent preclinical experiments and observational studies in patients after stroke suggest that the commercially available medication, Maraviroc, a CCR5 antagonist, may augment skills learning during rehabilitation training, especially during the first three months after onset, by affecting CREB and synaptic plasticity. The investigators will carry out a randomized controlled trial of Maraviroc in patients with disabilities severe enough to have required inpatient stroke rehabilitation and, based on our preclinical data, who can start the drug intervention within 6 weeks of stroke onset. The investigators will compare usual post-stroke care plus placebo versus Maraviroc given for 8 weeks in 60 participants. However, to try to maximize the amount of practice that is most relevant to the primary outcome measurements and determine whether or not Maraviroc can enhance the effects of training, as hypothesized, all participants will be tele-monitored by mobile health devices and will receive weekly telephonic encouragement, based on device data, to walk, reduce sedentary time, and reach and grasp in the home in between usual care therapies. Compliance, serial motor changes over time, and self-management skills in making use of the telerehabilitation devices will be a nested substudy of feasibility of remote monitoring and feedback.

NCT03172026 Stroke
MeSH: Stroke
HPO: Stroke

3 Interventions

Name: Maraviroc 300 mg

Description: FDA approved chemokine receptor (CCR5) inhibitor. Maraviroc will be started within two weeks of discharge from inpatient rehabilitation, which most often will occur from 4-6 weeks after stroke onset.

Type: Drug

Maraviroc + Augmented Rehabilitation

Name: Rehabilitation therapy

Description: All participants will have routine outpatient or home health physical and occupational therapy after inpatient discharge as prescribed by their physicians. Each group will be contacted weekly by phone to help maintain interest in the trial, count the number of usual care physical and occupational therapy completed, assure use of the assigned medication, ask about possible adverse reactions, and to encourage them to be active. The coordinator will obtain this information and provide the feedback using a standard script and checklist. A unique aspect of this trial is a telerehabilitation component that aims to give feedback to all participants to practice with the affected arm and walk daily.

Type: Behavioral

Maraviroc + Augmented Rehabilitation Placebo + Augmented Rehabilitation

Name: Placebo 300 mg

Description: Matched placebo will be started within two weeks of discharge from inpatient rehabilitation, which most often will occur from 4-6 weeks after stroke onset.

Type: Drug

Placebo + Augmented Rehabilitation


Primary Outcomes

Description: Timed walking speed over 10 meters. The evaluable sample size of 30 in each group will have 80% power to detect a difference in means of -0.206 (m/s), the difference between an assumed usual care walking speed of 0.51 (SD=0.28) and an assumed intervention group mean walking speed of 0.716. This assumes a common standard deviation in the two groups and a two group t-test with a 0.05 two-sided significance level. The estimates for the mean and standard deviation for walking speed come from the LEAPS RCT (Duncan, N Engl J Med, 2011). The t-test used for the power calculation is a simplification of the mixed effects analysis plan for the primary endpoints.

Measure: 10 Meter Walk Test

Time: Baseline, 6 months post

Description: Assessment of upper extremity function. Our sample size of 30 for each group is based on a statistical power of 80% with an alpha of 5% for detecting a meaningful difference of 6 points, i.e., a 10% change, which has been suggested by several completed trials. In a stroke trial, the standard deviation was 8 points measured at 2 weeks post stroke.

Measure: Action Research Arm Test

Time: Baseline, 6 months post

Secondary Outcomes

Description: Assessment of arm and leg impairment after stroke

Measure: Fugl-Meyer Motor score

Time: Baseline, within 5 days of last medication dose (8 weeks), at 6 months post stroke

Description: Self-report questionnaire on quality of life post-stroke

Measure: Stroke Impact Scale

Time: Baseline, within 5 days of last medication dose (8 weeks), at 6 months post stroke

Description: Distance walked in a 6 minute time period

Measure: 6 minute walking distance

Time: Baseline, within 5 days of last medication dose (8 weeks), at 6 months post stroke

Description: Self-report questionnaire related to exercise enjoyment

Measure: Physical Activity Enjoyment Scale

Time: Baseline, within 5 days of last medication dose (8 weeks), at 6 months post stroke

Description: Self-report questionnaire related to confidence in increasing activity and maintaining exercise routines

Measure: Activity Self Efficacy

Time: Baseline, within 5 days of last medication dose (8 weeks), at 6 months post stroke

Description: Self-report of activity levels

Measure: International Physical Activity Questionnaire

Time: Baseline, within 5 days of last medication dose (8 weeks), at 6 months post stroke

Description: Daily duration of bouts of walking

Measure: Walking activity, Sensors

Time: Collected daily for 8 weeks

Description: Total daily distance walked

Measure: Walking activity, Sensors

Time: Collected daily for 8 weeks

Description: Average daily walking speed

Measure: Walking activity, Sensors

Time: Collected daily for 8 weeks

Description: Sedentary time

Measure: Walking activity, Sensors

Time: Collected daily for 8 weeks

Description: Amount of time practicing

Measure: Upper extremity practice, Sensors

Time: Collected daily for 8 weeks

Description: Repetitions of task practice

Measure: Upper extremity practice, Sensors

Time: Collected daily for 8 weeks

Purpose: Treatment

Allocation: Randomized

Parallel Assignment


There is one SNP

SNPs


1 rs333

About 15% of the Ashkenazi Jewish population carries the deletion (CCR5 rs333 - 32).



HPO Nodes


HPO:
Stroke
Genes 117
MPL COL3A1 COL4A1 VHL TET2 TPP2 MYD88 COL5A1 FLNA TREX1 NPPA MYH11 HTRA1 ZMPSTE24 MYLK SH2B3 CLIP2 WFS1 CALR CYP11B1 MAT2A ACAD9 SMARCAL1 ACTA2 ACTB SLC19A2 GATA4 GATA6 ACTG1 BAZ1B DPM3 NR3C1 CPS1 ACVRL1 RFC2 APP GTF2IRD1 GDF2 ADA2 CBS MECP2 TTR ZAP70 ABCC6 NR2F2 NAGS SNAP29 STIM1 TGFB2 TGFB3 JAK2 TGFBR1 SLC2A10 TGFBR2 TGFBR3 CRELD1 MFAP5 MLXIPL ANGPTL6 LIMK1 OTC CCM2 FBN1 GTF2I THPO GLA PIGA TRNC LMNA COX1 COX2 COX3 GUCY1A1 PIK3C2A CYTB MTHFR LOX GYS1 JAG1 ND1 ND4 SCN5A ND5 AGXT ASS1 DYRK1B ND6 CST3 KCNQ1 TRNF TRNH ELN TRNK TRNL1 GNAQ PRKG1 RFT1 TRNQ PRKAG2 TRNS1 TRNS2 TRNV TRNW HBB ENG TNXB TBL2 MMUT PRNP TP53 NOTCH3 SMAD3 SMAD4 SON PCNT FOXE3 PMM2