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Efficacy and safety of a combined therapy in the symptomatic treatment of diabetic sensorimotor polyneuropathy - a prospective, randomized, controlled, parallel group, double-blind, double-dummy 3-arm trial (ARIEL)
EU CTIS ID: 2025-521985-82-00
What this study is testing
To assess whether a 16-week combined treatment provides superior effects on symptoms of diabetic sensorimotor polyneuropathy, compared to both pooled and individual monotherapies, based on a structured analytic strategy.
- Therapeutic exploratory (Phase II)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- Written informed consent signed by the participants prior to any performance of trial-related screening procedures
- Diagnosed mild to moderate symptomatic DSPN defined by abnormal or non-evocable sural nerve conduction velocity and/or abnormal or non-evocable sural nerve action potential AND DSPN symptoms (signified by NTSS-6 >6) AND neuropathic signs (signified by NDS of 3-8)
- HbA1c ≤9.5 % at screening or at a time point between screening and randomization.
- Willingness to avoid lifestyle changes or changes of diet during the trial (including start of drugs supporting weight loss)
- Participants must have completed and documented their baseline symptom assessment over seven consecutive days and the NTSS-6 questionnaire on the final day of symptom assessment, using the provided ePRO link, in accordance with the protocol-defined schedule within the seven days prior to the randomization visit
- Ability to follow trial restrictions
You likely can't join if
- Female participants with child-bearing potential not using any of the following effective birth control methods at least 2 months prior to randomization: a) oral contraceptives with a stable regimen; b) depomedroxyprogesterone; c) a double barrier method (either combining physical barrier methods e.g. condoms and diaphragm, or combining a physical barrier with a chemical barrier method, e.g. diaphragm/ condoms with spermicides); d) intrauterine device
- Treatment with glucagon-like peptide-1 receptor agonists (GLP-RA) within the last 12 months prior to randomization
- Any pharmacological treatment of chronic pain within the last 2 months prior to randomization. Exception is monotherapy with gabapentin up to 3000 mg/day, pregabalin up to 450 mg/day, or duloxetine up to 60 mg/day, without dose change within 2 months before randomization. For analgesia, standard doses of salicylates, ibuprofen or phenylacetic acid derivatives are allowed over a period of maximal 7 consecutive days, as well as rescue medication with paracetamol up to 3 g/day. Stable acetylsalicylic acid therapy in low doses for blood thinning purposes is also allowed
- Any contraindication to the use of the trial medication, including known allergy/hypersensitivity
- Significant hepatic disease (AST or ALT ≥3 times of upper limit of normal)
- Significant renal disease (eGFR <30 ml/min/1.73m2)
See the full eligibility criteria
Who can join
- Written informed consent signed by the participants prior to any performance of trial-related screening procedures
- Diagnosed mild to moderate symptomatic DSPN defined by abnormal or non-evocable sural nerve conduction velocity and/or abnormal or non-evocable sural nerve action potential AND DSPN symptoms (signified by NTSS-6 >6) AND neuropathic signs (signified by NDS of 3-8)
- HbA1c ≤9.5 % at screening or at a time point between screening and randomization.
- Willingness to avoid lifestyle changes or changes of diet during the trial (including start of drugs supporting weight loss)
- Participants must have completed and documented their baseline symptom assessment over seven consecutive days and the NTSS-6 questionnaire on the final day of symptom assessment, using the provided ePRO link, in accordance with the protocol-defined schedule within the seven days prior to the randomization visit
- Ability to follow trial restrictions
- Ability to attend scheduled visits at the Investigator site for the duration of the trial.
- Existence of a possibility to receive SMS
- Male or female participants ≥18 years old at the time of screening
- Diagnosed diabetes type 1 or 2 (per American Diabetes Association criteria (ADA Standards of Care in Diabetes 2025)), with diagnosis established at least 1 year prior to screening
- Stable diabetes medication use (or stable insulin dose for insulin-dependent participants) in the last 3 months prior to screening, which is unlikely to be changed during the trial period, as judged by the investigator. In case of therapy with SGLT-2 inhibitors, the start of treatment must additionally be at least 26 weeks prior to screening
- Stable diabetes metabolism, defined as no metabolic decompensation within the last 3 months (severe hypoglycaemia with unconsciousness, hyperosmolar hyperglycemic state, or ketoacidosis) prior to randomisation
- Persistent or recurrent neuropathic symptoms (e.g., numbness, tingling, burning or stabbing pain, hypersensitivity) that have occurred at least within 3 months prior to randomization. These symptoms and their duration can be reported by the participant to the Investigator during anamnesis
What rules you out
- Female participants with child-bearing potential not using any of the following effective birth control methods at least 2 months prior to randomization: a) oral contraceptives with a stable regimen; b) depomedroxyprogesterone; c) a double barrier method (either combining physical barrier methods e.g. condoms and diaphragm, or combining a physical barrier with a chemical barrier method, e.g. diaphragm/ condoms with spermicides); d) intrauterine device
- Treatment with glucagon-like peptide-1 receptor agonists (GLP-RA) within the last 12 months prior to randomization
- Any pharmacological treatment of chronic pain within the last 2 months prior to randomization. Exception is monotherapy with gabapentin up to 3000 mg/day, pregabalin up to 450 mg/day, or duloxetine up to 60 mg/day, without dose change within 2 months before randomization. For analgesia, standard doses of salicylates, ibuprofen or phenylacetic acid derivatives are allowed over a period of maximal 7 consecutive days, as well as rescue medication with paracetamol up to 3 g/day. Stable acetylsalicylic acid therapy in low doses for blood thinning purposes is also allowed
- Any contraindication to the use of the trial medication, including known allergy/hypersensitivity
- Significant hepatic disease (AST or ALT ≥3 times of upper limit of normal)
- Significant renal disease (eGFR <30 ml/min/1.73m2)
- Uncontrolled hypertension (systolic blood pressure >160 mm Hg, or diastolic blood pressure >100 mm Hg), with or without anti-hypertensive medication
- A major cardiovascular event, such as myocardial infarction or stroke, or an acute malignant disease in the 12 months prior to randomization
- Severe or unstable depression or severe or unstable other psychiatric diseases with potential influence on trial endpoints, as judged by the Investigator
- Current treatment with antidepressants (except stable duloxetine or selective serotonin reuptake inhibitors)
- Any other existing medical conditions, likely to affect the trial measures, as judged by the Investigator
- Neuropathy of any cause other than diabetes (e.g. vitamin B12 deficiency-, chemotherapy-, toxin-, drug- or autoimmune-induced neuropathies, peripheral neuropathies induced by damages of the spinal cord), myopathy, or other neurological diseases that might interfere with trial endpoints
- Currently active or history of alcohol abuse (defined as a regular intake of more than 24 units of alcohol per week for men and 12 units of alcohol per week for women; one unit of alcohol equals approximately 250 mL of beer, 100 mL of wine or 35 mL of spirits)
- Current or history of regular use of recreational drugs (except history of occasional or experimental cannabis use in the past, with no evidence of dependence)
- Participation in another interventional clinical trial within 2 months preceding randomization. Participation in registries is allowed
- Living in the same household with another participant of this trial
- Pregnant or nursing women at screening
- Severe chronic pain of origin other than DPN which might interfere with the trial endpoints, based on medical history or physical examination (e.g. fibromyalgia).
- Bilateral lower extremity amputations (above the ankle). Individuals with unilateral lower extremity amputation may be included, provided that the remaining limb allows for reliable assessment of neuropathy-related endpoints and safe participation in study procedures
- History of a disease (including cardiovascular, pulmonary, gastrointestinal, hematologic, or endocrine disease, or malignancy) that could potentially cause neuropathic pain or symptoms
- Maximum neuropathic pain level > 9 over the previous 4 weeks on a NRS as assessed at screening
- Magnesium deficiency at screening which cannot be compensated until randomization
- Treatment lasting 5 days or longer with concomitant medication containing ALA, BEN B-vitamins, evening primrose oil, deproteinized hemoderivates of calf blood, or other drugs or supplements with potential influence on trial endpoints (e.g. antioxidants) within the last 2 months prior to randomization
- Treatment with cutaneous electrical nerve stimulation, muscle stimulation, or 8 % capsaicin patch within the last 2 months prior to randomization.
The study team makes the final eligibility decision.
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18-64 years, 65+ years. The study team makes the final eligibility decision.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.