Metabolic Syndrome, Paraplegia and Tetraplegia, Spinal Cord Injury, Traumatic Spinal Cord Injury
Conditions
Keywords
spinal cord injury, tetraplegia, paraplegia, metabolic syndrome
Brief summary
The purpose of this research study is to measure the tolerability and preliminary efficacy of a drug, galantamine, to treat metabolic syndrome (MetS) by reducing circulating inflammation in people with spinal cord injury (SCI). Galantamine is FDA-approved for the treatment of Alzheimer's disease. Here, the drug is considered experimental for the purposes of this study.
Interventions
DRUGGalantamine Hydrobromide Extended Release
Galantamine hydrobromide extended release (ER) capsules, 8mg, administered orally once daily in the morning with a meal. Aim 1: Single 8mg dose in the laboratory with at least 5 hours of observation. Aim 2: 8mg once daily for Weeks 1-4; dose escalated to 16mg once daily (two 8mg capsules) for Weeks 5-12 based on tolerability. If the 16mg dose is not tolerated, the participant returns to 8mg daily. Total treatment duration: 12 weeks.
Sponsors
Northwell Health
Bronx Veterans Medical Research Foundation, Inc
Kessler Institute for Rehabilitation
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is an exploratory, three-site, parallel group, open-label study to evaluate tolerability and preliminary efficacy of galantamine to treat MetS via reduction of systemic inflammation in people with chronic SCI (tetraplegia or paraplegia). Participants with tetraplegia or paraplegia will be analyzed separately as independent groups.
Eligibility
Sex/Gender
ALL
Age
21 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Adults aged 21-75 years (male or female) * Chronic (≥1 year post injury) traumatic non-progressive spinal cord injury (SCI) * Wheelchair user for community mobility * Injury level of tetraplegia (cervical level) or paraplegia (all levels) * SCI-specific obesity indicated by waist circumference ≥94 cm * Resting heart rate \>45 bpm based on 10 measurements over 10 minutes * Without clinically significant cardiovascular abnormalities as indicated by 12-lead ECG * Tolerable bowel routine indicated by a score of \<10 on the International SCI Bowel Function Data Set (ISCI-BDS) * Metabolic Syndrome (MetS) defined by the presence of at least three of the following: (1) obesity indicated by SCI-specific waist circumference ≥94 cm, (2) elevated fasting glucose ≥100 mg/dL, (3) dyslipidemia: high triglycerides ≥150 mg/dL or low HDL cholesterol \<40 mg/dL for men and \<50 mg/dL for women, (4) C-reactive protein (CRP) levels \>1 mg/dL * Able to understand and communicate in English at the level of describing adverse event frequency and severity and completing validated outcome measures * Willingness to comply with all study procedures and availability for the duration of the study * Provision of signed and dated informed consent form
Exclusion criteria
* Diagnosis of neurological injury or condition other than SCI * Progressive condition that would be expected to change neurological status * Signs and symptoms of cardiovascular disease or cardiac arrhythmias * Resting heart rate \<45 bpm * Score of 10 or greater on the ISCI-BDS v2.1 indicating moderate to severe neurogenic bowel dysfunction * Severe concurrent medical disease, condition, or illness judged to be contraindicated by the site physician * Psychopathology documented in the medical record or history that may conflict with study objectives * Pregnancy (participant reported or determined by clinical lab test), women who plan to become pregnant, or women who are nursing during the study * Active cancer or currently in treatment for cancer * Triglyceride levels ≥400 mg/dL * Chronic use of medications with known or probable interactions with galantamine * Enrolled in another research study that is likely to interfere with conduct or results of the current study * Any other reason the site physician feels that participation is contraindicated
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in ISCI-BDS Neurogenic Bowel Symptoms Score (Aim 1 and Aim 2) | Visit 0 (Screening) through Visit 5 (Week 12) | Neurogenic bowel symptoms assessed using the International SCI Bowel Function Data Set (ISCI-BDS). Worsening will be defined as a negative change in ISCI-BDS score category (e.g., mild to moderate). |
| Change in Heart Rate (Avg) During In-Lab Observation (Aim 1) | Visit 1 (Day 1; pre-dose through 5 hours post-dose) | Heart rate (beats per minute) measured before administration of galantamine 8mgER and at 15-minute intervals during the in-lab observation period. |
| Change in Blood Pressure During In-Lab Observation (Aim 1) | Visit 1 (Day 1; pre-dose through 5 hours post-dose) | Blood pressure (mmHg) measured in the seated position before administration of galantamine 8mgER and at 15-minute intervals during the in-lab observation period. |
| Occurrence of Adverse Events During In-Lab Observation (Aim 1) | Visit 1 (Day 1; pre-dose through 5 hours post-dose) | Frequency and severity of all adverse events (AEs) during the in-lab observation period after a single dose of galantamine 8mgER, assessed by standardized AE survey and open-ended questions. AEs are graded using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The number of participants experiencing at least one AE will be reported. |
| Change in Heart Rate (Avg) During Outpatient Treatment (Aim 2) | Visit 2 (Day 2) through Visit 5 (Week 12) | Heart rate (beats per minute) measured at each study visit and daily at home. |
| Change in Blood Pressure During Outpatient Treatment (Aim 2) | Visit 2 (Day 2) through Visit 5 (Week 12) | Blood pressure (mmHg) will be measured at each study visit and daily at home |
| Occurrence of Adverse Events During Outpatient Treatment (Aim 2) | Visit 2 (Day 2) through Visit 5 (Week 12) | Frequency and severity of all adverse events (AEs) during the 12-week outpatient dose escalation period, assessed at each study visit and via weekly phone calls. AEs are graded using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 by severity and relationship to study drug. The number of participants experiencing at least one AE will be reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Inflammatory Cytokines During Outpatient Treatment (Aim 2) | Visit 2 (Day 2) and Visit 5 (Week 12) | Inflammatory markers such as: TNF-α, IL-1ß, IL-6, IL-10, and other cytokines (pg/ml) will be measured in plasma at Visit 2 (Day 2) and Visit 5 (Week 12) |
| Change in Plasma Leptin During Outpatient Treatment (Aim 2) | Visit 2 (Day 2) and Visit 5 (Week 12) | Plasma leptin levels measured (pg/ml) at Visit 2 (Day 2) and Visit 5 (Week 12) |
| Change in Plasma Adiponectin During Outpatient Treatment (Aim 2) | Visit 2 (Day 2) and Visit 5 (Week 12) | Plasma adiponectin levels (µg/mL) measured at Visit 2 (Day 2) and Visit 5 (Week 12) |
| Change in Lipids (HDL, LDL, and Triglycerides) | Visit 0 (Screening) and Visit 5 (Week 12) | High-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides (mg/dL) will be measured at Visit 0 (Screening) and Visit 5 (Week 12) |
| Change in Fasting Plasma Insulin | Visit 0 (Screening) and Visit 5 (Week 12) | Fasting plasma insulin levels (µIU/mL) measured at Visit 0 (Screening) and Visit 5 (Week 12) |
| Change in Fasting Blood Glucose | Visit 0 (Screening) and Visit 5 (Week 12) | Fasting blood glucose levels (mg/dL) measured at Visit 0 (Screening) and Visit 5 (Week 12) |
| Change in HOMA-IR From Screening (Aim 2) | Visit 0 (Screening) and Visit 5 (Week 12) | Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) calculated from fasting glucose and fasting insulin (Unitless index ) at Visit 0 (Screening) and Visit 5 (Week 12) |
| Change in HbA1c From Screening | Visit 0 (Screening) and Visit 5 (Week 12) | Hemoglobin A1c (HbA1c) levels (%) measured at Visit 0 (Screening) and Visit 5 (Week 12) |
| Change in C-Reactive Protein (CRP) | Visit 0 (Screening) and Visit 5 (Week 12) | C-reactive protein (CRP) levels (mg/L ) measured at Visit 0 (Screening) and Visit 5 (Week 12) |
| Change in Body Composition by DXA During Outpatient Treatment (Aim 2) | Visit 2 (Day 2) and Visit 5 (Week 12) | Total body fat mass (kg) and total body fat percentage measured by dual-energy X-ray absorptiometry (DXA) total body scan at Visit 2 (Day 2) and Visit 5 (Week 12) |
| Change in Waist and Hip Circumference During Outpatient Treatment (Aim 2) | Visit 2 (Day 2) and Visit 5 (Week 12) | Waist and Hip circumference (cm) measured by tape measure at Day 2 and at Week 12. |
| Change in High Frequency Heart Rate Variability (HF-HRV) During Outpatient Treatment (Aim 2) | Visit 2 (Day 2), Visit 3 (Week 4), Visit 4 (Week 8), and Visit 5 (Week 12) | High frequency component of heart rate variability (HF-HRV), a valid estimate of cardio-vagal tone (ms²) measured during supine and seated observations Visit 2 (Day 2), Visit 3 (Week 4), Visit 4 (Week 8), and Visit 5 (Week 12) |
Countries
United States
Contacts
CONTACTOna Bloom, PhD
Outcome results
None listed