Diabetes type 2: neuropathic symptoms
Conditions
Interventions
Product Name: ARA 290
Product Code: ARA 290
Pharmaceutical Form: Lyophilisate for solution for injection
INN or Proposed INN: Innate repair activator peptide
Current Sponsor code: ARA 290
Concentratio
Sponsors
Leiden University Medical Center
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Established diagnosis of diabetes mellitus type 2 Screening HbA1c between 7.5 % and 10 % inclusive [retest of HbA1c allowed for patients with borderline values] Quantitative sensory testing shows allodynia and altered temperature thresholds Spontaneous discomfort level of 6 or greater on Pain Now (Pain Detect; 0 (least discomfort)-10 (worst discomfort)) and small fiber neuropathy screening list (SFNSL; [1]) > 22, or spontaneous discomfort level on Pain Now (Pain Detect) 44 at screening AND at first dosing visit. Discomfort defined as distal pain/discomfort plus one of the following: 1) paresthesia 2) burning/painful feet worsening at night, or 3) intolerance of sheets or clothes touching the legs or feet Be able to read and understand the written consent form, complete study-related procedures, and communicate with the study staff Be willing to comply with study restrictions Be willing to check in with the study center via the telephone Between 18 and 70 years of age (inclusive) Body Mass Index (BMI) 8% at screening, able to visit the hospital sober Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 88 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 88
Exclusion criteria
Exclusion criteria: Clinically relevant abnormal history of physical and mental health other than conditions related to diabetes, as determined by medical history taking (as judged by the investigator) Clinically relevant abnormal laboratory results, vital signs, or physical findings other than conditions related to diabetes (as judged by the investigator) Known clinically relevant abnormalities in ECG (as judged by the investigator) Episodes of significant hypoglycemia (as judged by the investigator) Illicit drug abuse or excessive alcohol consumption (as judged by the investigator) History of serious malignancy (as judged by the investigator) History of severe allergies, or has had an anaphylactic reaction or significant intolerability to prescription or non-prescription drugs or food (as judged by the investigator) Subjects that received a vaccination or immunization within the month prior to screening. Anti-TNF therapy or other biological anti-inflammatory agents administered within the 6 months prior to screening. Use of erythropoiesis stimulating agents within the two months prior to screening or during the trial Participation in an investigational drug trial in the 3 months prior to administration of the initial dose of study drug or more than 4 times per year Inadequate venous accessibility as judged by clinicians (physician or nurse) Inability or unwillingness to self-administer ARA 290 via subcutaneous injections (or not have access to home health care for assistance in administration; also see 6.9) If female, pregnant or breast-feeding Any other condition that in the opinion of the investigator would complicate or compromise the study, or the well being of the patient
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary purpose of this double blind study is to determine the effect of ARA 290 on neuropathic symptoms in patients with type 2 diabetes. Amendment(Jul2014): 1) to determine insulin oscillations, 2) to determine whether ARA 290 administration increases insulin secreted to a glucose stimulus in a dose dependent manner as in the GK rat model and 3) whether extending the period of daily administration of ARA 290 to three months improves further glucose and lipid control and neuropathic symptoms in diabetic patients with small fiber neuropathy and whether these improvements are accompanied by improved systemic insulin oscillations;Secondary Objective: Secondary objectives are to assess the effects of ARA 290 on general health and well-being, quantitative sensory testing, intra epidermal nerve fiber densities, cardiac autonomic neuropathy (as determined by R-R AND QT interval variability/changes in the ECG), 6 minute walk test, and visual acuity as determined by ETDRS chart evaluation in these patient populations. Additionally, the effect of ARA 290 on glucose control and microalbuminuria will be assessed.;Primary end point(s): Collection of adverse events, serious adverse events, and laboratory parameters Change in hemoglobin A1c at day 28 and 56 compared to baseline Change in the scores of the Small Fiber Neuropathy Screening List, Pain Detect, and RAND-36 (pain and physical function components) at days 28, 56, and 84 compared to screening Amendment (Jul2014): Insulin oscillations, Intravenous Glucose Tolerance Test over 2 hours with frequently-sampled plasma glucose and insulin concentrations with ARA 290 4 mg administered during the course of the GTT . ;Timepoint(s) of evaluation of this end point: Pre-treatment, day 28, day 56 and day 84 Insulin oscillations: sample every 2 minutes for one hour | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Change in quantitative sensory testing at day 28 baseline Change in intra epidermal nerve fiber density at day 28 baseline Change in the 6 minute walk test at day 28 versus baseline Change in visual acuity at day 28 versus baseline Change in heart rate variability (R-R and QT intervals) at day 28 versus baseline Change in visual acuity at 28 and 56 days versus baseline Additionally, the effect of ARA 290 on glucose control, C reactive protein, and microalbuminuria in patients with diabetes will be assessed.change in fasting glucose at day 28 versus screening ;Timepoint(s) of evaluation of this end point: Pre-treatment, day 28, day 56 | — |
Countries
Netherlands
Contacts
Public ContactPrincipal Investigator
Leiden University Medical Center
Outcome results
None listed