Diabetic Peripheral NeuropathyPhase 2NCT07036796
Effect of Melatonin in Patients With Diabetic Peripheral Neuropathy
A Phase 2 study testing Melatonin in people with Diabetic Peripheral Neuropathy and Diabetic Neuropathy, run by Ain Shams University at 1 site in Egypt.
Trial summary
The aim of the current study is to measure the effect of melatonin as adjunct therapy on oxidative stress, inflammatory markers and clinical outcome in type 2 diabetic patients with diabetic peripheral neuropathy. Read more about this study
- Who is it for?
- Ages 40 to 75 years
- Conditions the study is for
- Diabetic Peripheral Neuropathy, Diabetic Neuropathy, Diabetic Peripheral Neuropathy in Type 2 Diabetic Patients
- What is being tested?
- Melatonin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteEgypt
- Study dates
- 4 Jul 2025to 4 Jul 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients aged 40-75 years diagnosed with type 2 DM.
- Diabetes duration at least 1 year.
- Patients diagnosed with diabetic peripheral neuropathy.
- Stable antidiabetic medication for at least 1 month before enrollment and during the trial
Who cannot join
- Patients with autoimmune disorders (such as lupus and rheumatoid arthritis), thyroid diseases, peripheral arterial disease and cancer patients.
- Patients with severe kidney or liver dysfunction.
- Patients diagnosed with neurodegenerative diseases.
- Active infection.
- Use of medications or supplements known to cause or treat peripheral neuropathy.
- Alcohol consumption or substance abuse.
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- Patients consuming any antioxidant supplements or anti-inflammatory medicines during or 3 months before enrollment.
- Pregnancy or lactation or expecting to get pregnant during the study.
- Allergy to melatonin.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Egypt1 site, 1 recruiting
- Recruiting
Ain Shams University hospital
Cairo
Manar Magdy Demonstrator at ain shams university, 01113177801, manar.magdy17@pharma.asu.edu.eg
About this study
Official title: Effect of Melatonin on the Clinical Outcomes in Type 2 Diabetic Patients With Peripheral Neuropathy
The aim of the current study is to measure the effect of melatonin as adjunct therapy on oxidative stress, inflammatory markers and clinical outcome in type 2 diabetic patients with diabetic peripheral neuropathy.
Read the detailed description
Diabetic neuropathy is a microvascular complication affecting 50% of patients throughout their lifetime. It leads to various complications including foot ulcerations and lower limb amputations, thus impairs the patient's quality of life. Distal symmetrical polyneuropathy is the most common subtype. Symptoms include tingling, burning and electrical pain associated with nocturnal exacerbation. Almost 50% of patients are asymptomatic thus diagnosis must include assessment of signs.
Pathophysiologic mechanism behind hyperglycemia induced nerve damage include the activation of various pathways including polyol and advanced glycation end product (AGE), which produces reactive oxygen species. Molecular studies have revealed the involvement of certain transcriptional regulators such as Nrf2-Keap1 and NfKb inflammatory cascade.
Nuclear erythroid growth factor-2 (Nrf2) functions primarily as a defense mechanism in cellular oxidative stress, producing anti-oxidant enzymes as glutathione reductase (GSH) and superoxide dismutase (SOD). However, in long term hyperglycemia, downregulation of nrf2 takes place, leading to accumulation of reactive oxygen species (ROS), which in turn activates nfkb inflammatory pathway and produces various cytokines such as tumor necrosis factor-alpha (Tnf-alpha), interleukin-1 (IL-1) and interleukin-6 (IL-6). Tumor-necrosis factor is known to be highly associated with nerve damage.
Drugs that target disease pathophysiology are currently unavailable, instead DPN management mainly depends on lifestyle modification through weight loss, blood pressure, blood glucose, lipid profile management along with symptomatic care. Yet these fail to stop disease progression.
Melatonin is known to possess anti-oxidant and anti-inflammatory properties through upregulating nrf2. It's hypothesized that adding it to standard therapy shall activate nrf2, and downregulate nfkb pathway and inflammatory cytokines, improving disease progression and patient's quality of life.
The aim of the current study is to measure the effect of melatonin on oxidative stress, inflammatory markers and clinical outcome in type 2 diabetic patients with DPN.
All patients will be assessed for the following data at baseline:
- Age, gender, diabetes duration, diabetic neuropathy duration.
- HbA1c, liver functions, kidney functions and lipid profile.
Lab assessment will be done at both baseline and at the end of the trial to assess the effect of melatonin on the following:
- Nuclear erythroid related factor-2 (NRf2) (an oxidative marker)
- Tumor necrosis factor-alpha (an inflammatory marker)
Assessment of clinical outcomes will be done as well, at both baseline and endpoint using the following:
- Toronto clinical scoring system (TCSS)
- Michigan neuropathy screening instrument questionnaire (MNSIQ) Samples used to assess oxidative and inflammatory markers will be stored at -80 degrees to be analyzed later at the end of the study using ELISA kits.
- Conditions
- Diabetic Peripheral Neuropathy, Diabetic Neuropathy, Diabetic Peripheral Neuropathy in Type 2 Diabetic Patients
- Being tested
- Melatonin
- Keywords
- Diabetic peripheral neuropathy, Diabetic neuropathies, Diabetic neuropathy in type 2 diabetes, Melatonin
- Medical subject headings
- Diabetic Neuropathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MelatoninDrug
Melatonin (N-acetyl-5-methoxytryptamine), also called the hormone of darkness, secreted primarily by the pineal gland. Possesses antioxidant, anti-inflammatory, anti-diabetic and neuroprotective effects. All of which could be explained by its activation of Nrf2 signaling pathway.
Melatonin administration has shown to improve motor nerve conduction velocity and nerve blood flow, reduce the levels of pro-inflammatory cytokines, reinforce antioxidant defense, and decrease DNA fragmentation through upregulating nrf2 pathway, when tested in mice with diabetic peripheral neuropathy. Moreover, early treatment with melatonin has shown to prevent developing diabetic neuropathy in streptozotocin induced diabetic mice.
| Study group | Role | What they receive |
|---|---|---|
| Group 1: Melatonin group | Active comparator | Group 1: Melatonin group (n=30) Patients will receive 10 mg (2 5mg Capsules) 1 hour before bedtime for 12 weeks, in addition to the standard therapy. Receives: Drug: Melatonin |
| Group 2: control group | No intervention | Group 2: No intervention, (n=30) patients will receive only standard therapy for 12 weeks |
What is being measured
The primary outcome is the main question the study is designed to answer.
Concentration of human nuclear factor erythroid 2-related factor (Nrf2)
Oxidative stress marker
Measured: Change from baseline human Nuclear factor erythroid 2-related factor at 3 months.
Secondary outcomes (5)
Concentration of Tumor necrosis factor alpha
Inflammatory marker
Measured: Change from baseline Tumor necrosis factor alpha at 3 months
Michigan neuropathy screening instrument questionnaire (MNSI-Q)
A questionnaire of 15 yes or no questions, a score of 7 or more means more neuropathic symptoms
Measured: At baseline and after 3 months
Toronto clinical scoring system (TCSS)
A scoring system used to assess symptoms, reflexes and signs, as score increases indicates more neuropathy.
Measured: At baseline and after 3 months
Diabetic neuropathy score (DNS)
A score used to assess the major symptoms of DPN.
Measured: At baseline and after 3 months
D-39 questionnaire
A questionnaire used to test the effect of diabetes on patient's quality of life.
Measured: At baseline and after 3 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jun 2025
- Study start4 Jul 2025
- Primary completion4 Jul 2027 (estimated)
- Study completion4 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetic Peripheral NeuropathyStudies of the same condition, open and under way.
- More trials run by Ain Shams UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Prospective Randomized controlled clinical trial open label
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ain Shams University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, manar magdy, Ain Shams University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07036796
- Sponsor's protocol ID
- RHDIRB2020110301 REC#310
- Status last verified
- Jul 2026
- First submitted
- 17 Jun 2025
- Last updated
- 21 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 21 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Melatonin on the Clinical Outcomes in Type 2 Diabetic Patients With Peripheral Neuropathy
- ClinicalTrials.gov ID
- NCT07036796
- Acronym / sponsor ID
- RHDIRB2020110301 REC#310
- Conditions
- Diabetic Peripheral Neuropathy, Diabetic Neuropathy, Diabetic Peripheral Neuropathy in Type 2 Diabetic Patients
- Keywords
- Diabetic peripheral neuropathy, Diabetic neuropathies, Diabetic neuropathy in type 2 diabetes, Melatonin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Ain Shams UniversityUniversity, hospital or other
- Study start
- 4 Jul 2025 (actual)
- Primary completion
- 4 Jul 2027 (estimated)
- Study completion
- 4 Jul 2027 (estimated)
- First posted
- 25 Jun 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of the current study is to measure the effect of melatonin as adjunct therapy on oxidative stress, inflammatory markers and clinical outcome in type 2 diabetic patients with diabetic peripheral neuropathy.
Detailed description
Diabetic neuropathy is a microvascular complication affecting 50% of patients throughout their lifetime. It leads to various complications including foot ulcerations and lower limb amputations, thus impairs the patient's quality of life. Distal symmetrical polyneuropathy is the most common subtype. Symptoms include tingling, burning and electrical pain associated with nocturnal exacerbation. Almost 50% of patients are asymptomatic thus diagnosis must include assessment of signs.
Pathophysiologic mechanism behind hyperglycemia induced nerve damage include the activation of various pathways including polyol and advanced glycation end product (AGE), which produces reactive oxygen species. Molecular studies have revealed the involvement of certain transcriptional regulators such as Nrf2-Keap1 and NfKb inflammatory cascade.
Nuclear erythroid growth factor-2 (Nrf2) functions primarily as a defense mechanism in cellular oxidative stress, producing anti-oxidant enzymes as glutathione reductase (GSH) and superoxide dismutase (SOD). However, in long term hyperglycemia, downregulation of nrf2 takes place, leading to accumulation of reactive oxygen species (ROS), which in turn activates nfkb inflammatory pathway and produces various cytokines such as tumor necrosis factor-alpha (Tnf-alpha), interleukin-1 (IL-1) and interleukin-6 (IL-6). Tumor-necrosis factor is known to be highly associated with nerve damage.
Drugs that target disease pathophysiology are currently unavailable, instead DPN management mainly depends on lifestyle modification through weight loss, blood pressure, blood glucose, lipid profile management along with symptomatic care. Yet these fail to stop disease progression.
Melatonin is known to possess anti-oxidant and anti-inflammatory properties through upregulating nrf2. It's hypothesized that adding it to standard therapy shall activate nrf2, and downregulate nfkb pathway and inflammatory cytokines, improving disease progression and patient's quality of life.
The aim of the current study is to measure the effect of melatonin on oxidative stress, inflammatory markers and clinical outcome in type 2 diabetic patients with DPN.
All patients will be assessed for the following data at baseline:
- Age, gender, diabetes duration, diabetic neuropathy duration.
- HbA1c, liver functions, kidney functions and lipid profile.
Lab assessment will be done at both baseline and at the end of the trial to assess the effect of melatonin on the following:
- Nuclear erythroid related factor-2 (NRf2) (an oxidative marker)
- Tumor necrosis factor-alpha (an inflammatory marker)
Assessment of clinical outcomes will be done as well, at both baseline and endpoint using the following:
- Toronto clinical scoring system (TCSS)
- Michigan neuropathy screening instrument questionnaire (MNSIQ) Samples used to assess oxidative and inflammatory markers will be stored at -80 degrees to be analyzed later at the end of the study using ELISA kits.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Prospective Randomized controlled clinical trial open label
| Arm | Type | Receives |
|---|---|---|
| Group 1: Melatonin group | Active comparator | Drug: MelatoninGroup 1: Melatonin group (n=30) Patients will receive 10 mg (2 5mg Capsules) 1 hour before bedtime for 12 weeks, in addition to the standard therapy. |
| Group 2: control group | No intervention | –Group 2: No intervention, (n=30) patients will receive only standard therapy for 12 weeks |
Who may qualify
- Ages
- 40 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Patients aged 40-75 years diagnosed with type 2 DM.
- Diabetes duration at least 1 year.
- Patients diagnosed with diabetic peripheral neuropathy.
- Stable antidiabetic medication for at least 1 month before enrollment and during the trial
Key exclusion criteria (9 listed)
- Patients with autoimmune disorders (such as lupus and rheumatoid arthritis), thyroid diseases, peripheral arterial disease and cancer patients.
- Patients with severe kidney or liver dysfunction.
- Patients diagnosed with neurodegenerative diseases.
- Active infection.
- Use of medications or supplements known to cause or treat peripheral neuropathy.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MelatoninMelatonin (N-acetyl-5-methoxytryptamine), also called the hormone of darkness, secreted primarily by the pineal gland. Possesses antioxidant, anti-inflammatory, anti-diabetic and neuroprotective effects. All of which could be explained by its activation of Nrf2 signaling pathway. Melatonin administration has shown to improve motor nerve conduction velocity and nerve blood flow, reduce the levels of pro-inflammatory cytokines, reinforce antioxidant defense, and decrease DNA fragmentation through upregulating nrf2 pathway, when tested in mice with diabetic peripheral neuropathy. Moreover, early treatment with melatonin has shown to prevent developing diabetic neuropathy in streptozotocin induced diabetic mice. | Drug | Group 1: Melatonin group |
Primary outcome
Concentration of human nuclear factor erythroid 2-related factor (Nrf2)
Time frame: Change from baseline human Nuclear factor erythroid 2-related factor at 3 months.
Oxidative stress marker
5 secondary outcomes
Concentration of Tumor necrosis factor alpha
Time frame: Change from baseline Tumor necrosis factor alpha at 3 months
Michigan neuropathy screening instrument questionnaire (MNSI-Q)
Time frame: At baseline and after 3 months
Toronto clinical scoring system (TCSS)
Time frame: At baseline and after 3 months
Diabetic neuropathy score (DNS)
Time frame: At baseline and after 3 months
D-39 questionnaire
Time frame: At baseline and after 3 months.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Jul 2026.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Melatonin in people with Diabetic Peripheral Neuropathy and Diabetic Neuropathy, run by Ain Shams University at 1 site in Egypt.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 21 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Concentration of human nuclear factor erythroid 2-related factor (Nrf2) (time frame: Change from baseline human Nuclear factor erythroid 2-related factor at 3 months.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jul 2026.