Diabetic NeuropathiesNCT05247034
Effect of Cocoa Supplementation Peripheral and Autonomic Diabetic Neuropathy
A study testing Cocoa in people with Diabetic Neuropathies, run by Anahuac University at 3 sites in Mexico.
Trial summary
Type 2 diabetes mellitus is a high incidence disease in Mexico and is associated with the development of chronic degenerative complications such as diabetic neuropathy. The latter manifests itself as a set of disorders that occur as a consequence of a chronic hyperglycemic state that can induce oxidative stress and… Read more about this study
- Who is it for?
- Ages 40 to 60 years
- Conditions the study is for
- Diabetic Neuropathies
- What is being tested?
- Cocoa
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 39 participants
- Where
- 3 sitesMexico
- Study dates
- 4 Jun 2021to 3 Sep 2024
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Adults aged 40-60 years with a diagnosis of type 2 diabetes mellitus and diabetic neuropathy
- Minimum time of diagnosis of T2DM of 5 years
- Who have a Michigan Neuropathy Screening Instrument (MNSI) score ≥2
- Male and Female
- Have them sign the informed consent letter
Who cannot join
- Subjects who modify their pharmacological treatment during the study
- Subjects who do not attend one of the intermediate consultations
Trial locations and contacts
3 sites in 1 country.
Mexico3 sites
Universidad Anáhuac México Norte
Huixquilucan, State of Mexico, 52786
Centro de Especialidades del Riñón
Naucalpan, State of Mexico, 53100
Clínica de Medicina Familiar "Nueva Oxtotitlán" ISSSTE
Toluca, State of Mexico, 50100
About this study
Official title: Evaluation of the Effect of Cocoa Supplementation on Biochemical and Clinical Profile and Sensory-motor Processing of Peripheral and Autonomic Diabetic Neuropathy: Randomized Clinical Trial
Type 2 diabetes mellitus is a high incidence disease in Mexico and is associated with the development of chronic degenerative complications such as diabetic neuropathy. The latter manifests itself as a set of disorders that occur as a consequence of a chronic hyperglycemic state that can induce oxidative stress and inflammation, resulting in damage to the autonomic and peripheral nervous system. In Mexico, it has been reported that this complication usually occurs between 29% and 90% of patients with diabetes.
Cocoa is a food with a high content of flavonoids, which are phenolic compounds with antioxidant and anti-inflammatory effects. Additionally, its consumption has been associated with a decrease in hyperglycemia and insulin resistance, improvement in mitochondrial function, and, based on the above, an effect on diabetic complications has been suggested; This has been demonstrated in in vivo and in vitro models, but not in the human population.
Read more
Once the symptoms of diabetic neuropathy have started, palliative treatments are prescribed, and to date there are no pharmacological compounds that have been shown to reverse the consequences of diabetic peripheral and autonomic neuropathy. Additionally, clinical trials of compounds with antioxidant properties have only performed subjective evaluations based on questionnaires on the perception of the improvement of diabetic neuropathy and some biochemical markers or nerve conduction tests, however, the results shown have not been conclusive.
This is why a double-blind, randomized controlled clinical trial is proposed, with the objective of evaluating the effect of cocoa supplementation in patients with type 2 diabetes mellitus and peripheral and autonomic diabetic neuropathy on a) the biochemical profile, which includes the evaluation of the glycemic and lipid profile, quantification of pro-inflammatory cytokines and oxidative stress markers; b) the clinical profile through the application of standardized questionnaires, anthropometric measurements and blood pressure, and c) somatosensory processing through the paired pulse H reflex test.
The hypothesis of this study is that cocoa supplementation will have a beneficial effect on the biochemical and clinical profile and somatosensory processing of peripheral and autonomic diabetic neuropathy.
Read the detailed description
Type 2 diabetes mellitus (T2DM) is a high incidence disease in Mexico and is associated with the development of chronic degenerative complications such as diabetic neuropathy. The latter manifests itself as a set of disorders that occur as a consequence of a chronic hyperglycemic state that can induce oxidative stress and inflammation, resulting in damage to the autonomic and peripheral nervous system. In Mexico, it has been reported that this complication usually occurs between 29% and 90% of patients with diabetes.
Cocoa is a food with a high content of flavonoids, which are phenolic compounds with antioxidant and anti-inflammatory effects. Additionally, its consumption has been associated with a decrease in hyperglycemia and insulin resistance, improvement in mitochondrial function, and, based on the above, an effect on diabetic complications has been suggested; This has been demonstrated in in vivo and in vitro models, but not in the human population.
Once the symptoms of diabetic neuropathy have started, palliative treatments are prescribed, and to date there are no pharmacological compounds that have been shown to reverse the consequences of diabetic peripheral and autonomic neuropathy. Additionally, clinical trials of compounds with antioxidant properties have only performed subjective evaluations based on questionnaires on the perception of the improvement of diabetic neuropathy and some biochemical markers or nerve conduction tests, however, the results shown have not been conclusive.
This is why a double-blind, randomized controlled clinical trial is proposed, with the objective of evaluating the effect of cocoa supplementation in patients with type 2 diabetes mellitus and peripheral and autonomic diabetic neuropathy on a) the biochemical profile, which includes the evaluation of the glycemic and lipid profile, quantification of pro-inflammatory cytokines and oxidative stress markers; b) the clinical profile through the application of standardized questionnaires, anthropometric measurements and blood pressure, and c) somatosensory processing through the paired pulse H reflex test. Hypothesis: The hypothesis of this study is that cocoa supplementation will have a beneficial effect on the biochemical and clinical profile and somatosensory processing of peripheral and autonomic diabetic neuropathy. Statistical analysis: For the evaluation of the intragroup variables, a statistical analysis will be carried out with ANOVA for repeated samples with Tukey's post hoc, or, where appropriate, Friedman with Dunn's post hoc, as well as Student's t for dependent groups, or in its case, with Wilcoxon. The intergroup comparison will be made with Student's T for independent samples, or if applicable, with Mann Whitney's U, considering p <0.05 as statistical significance and using the statistical software GraphPad Prism version 5.
The H reflex test will be performed by electrical stimulation through disposable surface electrodes connected to a constant current bipolar electrical stimulator (Digitimer DS8R). The recording of the electrophysiological signals will be carried out using surface electrodes connected to the signal acquisition and amplification system (LabChart and PowerLab 8/35, ADInstruments). The signals obtained will be sampled at 10 kilohertz (KHz) with a 0.5- 500 Hz band-pass filter. The signals will be stored in a computer for later analysis.
The placement of electrodes for stimulation will be carried out as follows: the active electrode (anode) at the level of the Achilles tendon, the positive electrode (cathode) above the inverted "v" between the calf muscles (gastrocnemius). Subsequently, the reference electrode will be placed at the level of the gastrocnemius heads. It will be stimulated behind the knee where the tibial nerve has its anatomical path.
The test will start with an intensity of 0 milliamp (mA) and then pulses will be given every 0.5 millivolts (mV) until the evoked potential (H reflex) is observed in a consistent and clearly identifiable way as a function of latency (35-45 ms). The electrical stimulus consists of the application of 1 square pulse (1 ms duration each pulse) every 10 seconds (10 pulses in total). The maximum intensity of the applied current will be according to the sensitivity and tolerance of the individual in both lower limbs during the tests on the sensory and motor nerves. The applied electrical pulse should not cause a painful sensation, but it can cause a tingling sensation. The test will be suspended if the individual reports pain or does not wish to continue with the research protocol. The "H" reflex test will be done in two parts. The first part of the protocol consists of determining the stimulus intensity vs. amplitude of motor responses from the appearance of the "M" wave and the "H" wave, for which the electric current will be increased in steps of 0.5 µA until the appearance of the waves. For this part, only one electrical pulse (1 ms duration) will be given every 10 seconds. The intensity of electrical current that will be used for the second part of the protocol will be that whose value in the amplitude curve of the H wave-electrical current intensity reaches 60% of the maximum amplitude. This stimulation value guarantees the reproducibility and minimum variability of this wave, which also prevents muscle contraction that contaminates the electrical register. The second part constitutes the paired electrical stimulation test in which two electrical pulses (1 ms in duration) will be produced at different frequencies between the pulses: 0.1, 1, 5 and 10 Hz. The interval between the paired pulses will be 10 s, until completing 10 series.
The electrophysiological recordings will be analyzed with the Clampfit 10.0 software. The latency and amplitude of the evoked potentials H1 and H2 will be determined for each electrical pulse and at all stimulation frequencies, taking the stimulus artifact as a reference. Subsequently, the ratio of the amplitude of the paired H2/H1 pulses will be determined to establish the modulation of spinal excitability. A ratio ≥0.6 for any stimulation frequency will be considered as an indicator of dysfunction in somatosensory processing according to Marshall et al.
- Conditions
- Diabetic Neuropathies
- Being tested
- Cocoa, Placebo
- Keywords
- Cocoa, Diabetic neuropathy, H-reflex, Cardiometabolic risk factor, Polyphenols, Antioxidants
- Medical subject headings
- Diabetic Neuropathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CocoaDietary supplement
Each capsule of cocoa powder contains 12.5 mg of flavonoids, providing a total of 50 mg per day.
PlaceboOther
Each capsule contains 500 mg of methylcellulose
| Study group | Role | What they receive |
|---|---|---|
| Intervention group | Experimental | Diet for patients with diabetes + 4 capsules of cocoa powder, 500 mg each, daily for 12 weeks. Receives: Dietary Supplement: Cocoa |
| Control group | Placebo comparator | Diet for patients with diabetes + 4 capsules of methylcellulose 500 mg each, daily for 12 weeks. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Toronto Clinical Scoring System (TCSS)
It is a system of clinical evaluations carried out by the researcher to identify peripheral neuropathy, assigning a score to symptomatology, reflexes and sensory tests.
For the purposes of this study, the total score, i.e., the sum of all units on the scale, is reported. The minimum score that can be obtained is 0 points, while the maximum is 19 points. This means that the higher the score, the greater the severity (no grades were established based on the severity of the neuropathy).
For the data represented in the row "Change from baseline at Week 12", it is the delta of the final measurement vs. the initial measurement, that is, the final measurement minus the baseline measurement.
Measured: At baseline and after 12 weeks
Secondary outcomes (17)
Rate-dependent Depression of the H-reflex
Rate-dependent depression (RDD) is a measure of change in amplitude of the Hoffman (H) reflex over consecutive stimulations. Rate-dependent depression is impaired after disinhibition of spinal sensory processing caused by spinal cord injury.
For the purposes of this study, the ratio of the amplitude of the pulses Hn/H1 ≥ 0.5 for stimulation frequencies 1, 5 and 10 Hz, was considered as an indicator of dysfunction in somatosensory processing. In healthy subjects, the ratio of the amplitude of the pulses Hn/H1 is expected to be <0.5.
Each subject received 5 pulses for each stimulation frequency, and the average for each subject was determined. The group average was then obtained for each stimulation frequency (1, 5, and 10 Hz).
For the data represented in the row "Change from baseline at Week 12", it is the delta of the final measurement vs. the initial measurement, that is, the final measurement minus the baseline measurement.
Measured: At baseline and after 12 weeks
BEST Questionnaire
The questionnaire includes 4 questions that refer to gastrointestinal symptoms. This questions are measured in a scale from 1 (better health status) to 5 (worse health status) and it is related to gastrointestinal autonomic diabetic neuropathy.
Final score: Minimum is 4 points (better health status) and maximum is 19 points (worse health status).
For the data represented in the row "Change from baseline at Week 12", it is the delta of the final measurement vs. the initial measurement, that is, the final measurement minus the baseline measurement.
Measured: At baseline, after 4, 8 and 12 weeks
Bristol Stool Form Scale
It is composed of categories that include an image and an explanation, ranging from 1 to 7, being 1 separate hard pieces, which pass with difficulty and 7 watery stools. It is related to gastrointestinal autonomic diabetic neuropathy.
The reported outcomes are the percentage of participants who had altered bristol stool form scale, that is, participants who were in categories 1, 2, 5, 6 and 7.
Measured: At baseline and 12 weeks
Weight
Weight of an individual in kg determined by the scale. The measurement is done without shoes and with as little clothing as possible. The subject must be placed in the center and remain still during the measurement.
For the data represented in the row "Change from baseline at Week 12", it is the delta of the final measurement vs. the initial measurement, that is, the final measurement minus the baseline measurement.
Measured: At baseline, after 4, 8 and 12 weeks
Waist Circumference
Waist circumference in cm: The measuring tape is placed in a horizontal plane around the waist, taking the midaxillary line as a reference, locating the midpoint between the lower costal margin and the highest lateral border of the iliac crest.
For the data represented in the row "Change from baseline at Week 12", it is the delta of the final measurement vs. the initial measurement, that is, the final measurement minus the baseline measurement.
Measured: At baseline, after 4, 8 and 12 weeks
Waist-to-Height Ratio
It is obtained by dividing the waist circumference in cm by the height in cm, with a result of ≥ 0.5 indicating an increased risk for cardiometabolic disease.
For the data represented in the row "Change from baseline at Week 12", it is the delta of the final measurement vs. the initial measurement, that is, the final measurement minus the baseline measurement.
Measured: At baseline, after 4, 8 and 12 weeks
Abdominal Circumference
Abdominal circumference in cm: The top of the hip bone and the top of the right iliac crest are located and the measuring tape is placed horizontally around the abdomen, at the level of the iliac crest, at the end of a normal expiration.
For the data represented in the row "Change from baseline at Week 12", it is the delta of the final measurement vs. the initial measurement, that is, the final measurement minus the baseline measurement.
Measured: At baseline, after 4, 8 and 12 weeks
Systolic Blood Pressure
A sphygmomanometer is used to obtain blood pressure with the technique specified in the Clinical Practice Guidelines for the diagnosis and treatment of arterial hypertension at the first level of care, it is measured in mmHg.
For the data represented in the row "Change from baseline at Week 12", it is the delta of the final measurement vs. the initial measurement, that is, the final measurement minus the baseline measurement.
Measured: At baseline, after 4, 8 and 12 weeks
Diastolic Blood Pressure
A sphygmomanometer is used to obtain blood pressure with the technique specified in the Clinical Practice Guidelines for the diagnosis and treatment of arterial hypertension at the first level of care, it is measured in mmHg.
For the data represented in the row "Change from baseline at Week 12", it is the delta of the final measurement vs. the initial measurement, that is, the final measurement minus the baseline measurement.
Measured: At baseline, after 4, 8 and 12 weeks
Glucose
Blood glucose concentration and is measured as mg/dL. For the data represented in the row "Change from baseline at Week 12", it is the delta of the final measurement vs. the initial measurement, that is, the final measurement minus the baseline measurement.
Measured: At baseline and after 12 weeks
Glycated Hemoglobin A1c
Value of the fraction of hemoglobin that has glucose attached and is reported in percentage (%).
For the data represented in the row "Change from baseline at Week 12", it is the delta of the final measurement vs. the initial measurement, that is, the final measurement minus the baseline measurement.
Measured: At baseline and after 12 weeks
Triglycerides
Blood triglycerides concentration and is measured as mg/dL. For the data represented in the row "Change from baseline at Week 12", it is the delta of the final measurement vs. the initial measurement, that is, the final measurement minus the baseline measurement.
Measured: At baseline and after 12 weeks
High-density Lipoprotein Cholesterol
Blood high-density lipoprotein cholesterol concentration and is measured as mg/dL.
For the data represented in the row "Change from baseline at Week 12", it is the delta of the final measurement vs. the initial measurement, that is, the final measurement minus the baseline measurement.
Measured: At baseline and after 12 weeks
Triglycerides/HDL Ratio
It is obtained after dividing the serum concentration of triglycerides in mg/dL by the serum concentration of HDL in mg/dL. It does not have units.
For the data represented in the row "Change from baseline at Week 12", it is the delta of the final measurement vs. the initial measurement, that is, the final measurement minus the baseline measurement.
Measured: At baseline and after 12 weeks
Low-density Lipoprotein Cholesterol
Blood low-density lipoprotein cholesterol concentration and is measured as mg/dL.
For the data represented in the row "Change from baseline at Week 12", it is the delta of the final measurement vs. the initial measurement, that is, the final measurement minus the baseline measurement.
Measured: At baseline and after 12 weeks
Neutrophil/Lymphocyte Ratio
It is obtained by dividing the serum concentration of the absolute number of neutrophils by the serum concentration of the absolute number of lymphocytes. Without unit.
For the data represented in the row "Change from baseline at Week 12", it is the delta of the final measurement vs. the initial measurement, that is, the final measurement minus the baseline measurement.
Measured: At baseline and after 12 weeks
Diabetes 39 Instrument
It is a self-administered instrument that allows patients to describe how their QOL was affected during the previous month in five domains: energy and mobility (15 questions), diabetes control (12 questions), anxiety and worry (4 questions), social impact (5 questions), and sexual behavior (3 questions). Responses are scored on a seven-point scale that ranged from "not affected at all" (score = 1) to "extremely affected" (score = 7). All responses are summed and it is applied a linear transformation to a 0-100 scale. Lower scores indicated a better QOL.
For the data represented in the row "Change from baseline at Week 12", it is the delta of the final measurement vs. the initial measurement, that is, the final measurement minus the baseline measurement.
Measured: At baseline and after 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Feb 2022
- Study start4 Jun 2021
- Primary completion30 Jun 2024
- Study completion3 Sep 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Diabetic NeuropathiesStudies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- Anahuac University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Rebeca Kababie Ameo, Anahuac University
- Investigators
- Carlos Cuéllar-Ramos, PhD, Study director, Anahuac UniversityGabriela Gutiérrez-Salmeán, PhD, Study director, Anahuac University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05247034
- Sponsor's protocol ID
- 202103
- Other IDs
- 202094
- Status last verified
- Apr 2025
- First submitted
- 5 Jan 2022
- Last updated
- 1 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Effect of Cocoa Supplementation on Biochemical and Clinical Profile and Sensory-motor Processing of Peripheral and Autonomic Diabetic Neuropathy: Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT05247034
- Acronym / sponsor ID
- 202103
- Conditions
- Diabetic Neuropathies
- Keywords
- Cocoa, Diabetic neuropathy, H-reflex, Cardiometabolic risk factor, Polyphenols, Antioxidants
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 39 participants (actual)
- Lead sponsor
- Anahuac UniversityUniversity, hospital or other
- Study start
- 4 Jun 2021 (actual)
- Primary completion
- 30 Jun 2024 (actual)
- Study completion
- 3 Sep 2024 (actual)
- First posted
- 18 Feb 2022 (actual)
- Results
- Posted 1 May 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Type 2 diabetes mellitus is a high incidence disease in Mexico and is associated with the development of chronic degenerative complications such as diabetic neuropathy. The latter manifests itself as a set of disorders that occur as a consequence of a chronic hyperglycemic state that can induce oxidative stress and inflammation, resulting in damage to the autonomic and peripheral nervous system. In Mexico, it has been reported that this complication usually occurs between 29% and 90% of patients with diabetes.
Cocoa is a food with a high content of flavonoids, which are phenolic compounds with antioxidant and anti-inflammatory effects. Additionally, its consumption has been associated with a decrease in hyperglycemia and insulin resistance, improvement in mitochondrial function, and, based on the above, an effect on diabetic complications has been suggested; This has been demonstrated in in vivo and in vitro models, but not in the human population.
Once the symptoms of diabetic neuropathy have started, palliative treatments are prescribed, and to date there are no pharmacological compounds that have been shown to reverse the consequences of diabetic peripheral and autonomic neuropathy. Additionally, clinical trials of compounds with antioxidant properties have only performed subjective evaluations based on questionnaires on the perception of the improvement of diabetic neuropathy and some biochemical markers or nerve conduction tests, however, the results shown have not been conclusive.
This is why a double-blind, randomized controlled clinical trial is proposed, with the objective of evaluating the effect of cocoa supplementation in patients with type 2 diabetes mellitus and peripheral and autonomic diabetic neuropathy on a) the biochemical profile, which includes the evaluation of the glycemic and lipid profile, quantification of pro-inflammatory cytokines and oxidative stress markers; b) the clinical profile through the application of standardized questionnaires, anthropometric measurements and blood pressure, and c) somatosensory processing through the paired pulse H reflex test.
The hypothesis of this study is that cocoa supplementation will have a beneficial effect on the biochemical and clinical profile and somatosensory processing of peripheral and autonomic diabetic neuropathy.
Detailed description
Type 2 diabetes mellitus (T2DM) is a high incidence disease in Mexico and is associated with the development of chronic degenerative complications such as diabetic neuropathy. The latter manifests itself as a set of disorders that occur as a consequence of a chronic hyperglycemic state that can induce oxidative stress and inflammation, resulting in damage to the autonomic and peripheral nervous system. In Mexico, it has been reported that this complication usually occurs between 29% and 90% of patients with diabetes.
Cocoa is a food with a high content of flavonoids, which are phenolic compounds with antioxidant and anti-inflammatory effects. Additionally, its consumption has been associated with a decrease in hyperglycemia and insulin resistance, improvement in mitochondrial function, and, based on the above, an effect on diabetic complications has been suggested; This has been demonstrated in in vivo and in vitro models, but not in the human population.
Once the symptoms of diabetic neuropathy have started, palliative treatments are prescribed, and to date there are no pharmacological compounds that have been shown to reverse the consequences of diabetic peripheral and autonomic neuropathy. Additionally, clinical trials of compounds with antioxidant properties have only performed subjective evaluations based on questionnaires on the perception of the improvement of diabetic neuropathy and some biochemical markers or nerve conduction tests, however, the results shown have not been conclusive.
This is why a double-blind, randomized controlled clinical trial is proposed, with the objective of evaluating the effect of cocoa supplementation in patients with type 2 diabetes mellitus and peripheral and autonomic diabetic neuropathy on a) the biochemical profile, which includes the evaluation of the glycemic and lipid profile, quantification of pro-inflammatory cytokines and oxidative stress markers; b) the clinical profile through the application of standardized questionnaires, anthropometric measurements and blood pressure, and c) somatosensory processing through the paired pulse H reflex test. Hypothesis: The hypothesis of this study is that cocoa supplementation will have a beneficial effect on the biochemical and clinical profile and somatosensory processing of peripheral and autonomic diabetic neuropathy. Statistical analysis: For the evaluation of the intragroup variables, a statistical analysis will be carried out with ANOVA for repeated samples with Tukey's post hoc, or, where appropriate, Friedman with Dunn's post hoc, as well as Student's t for dependent groups, or in its case, with Wilcoxon. The intergroup comparison will be made with Student's T for independent samples, or if applicable, with Mann Whitney's U, considering p <0.05 as statistical significance and using the statistical software GraphPad Prism version 5.
The H reflex test will be performed by electrical stimulation through disposable surface electrodes connected to a constant current bipolar electrical stimulator (Digitimer DS8R). The recording of the electrophysiological signals will be carried out using surface electrodes connected to the signal acquisition and amplification system (LabChart and PowerLab 8/35, ADInstruments). The signals obtained will be sampled at 10 kilohertz (KHz) with a 0.5- 500 Hz band-pass filter. The signals will be stored in a computer for later analysis.
The placement of electrodes for stimulation will be carried out as follows: the active electrode (anode) at the level of the Achilles tendon, the positive electrode (cathode) above the inverted "v" between the calf muscles (gastrocnemius). Subsequently, the reference electrode will be placed at the level of the gastrocnemius heads. It will be stimulated behind the knee where the tibial nerve has its anatomical path.
The test will start with an intensity of 0 milliamp (mA) and then pulses will be given every 0.5 millivolts (mV) until the evoked potential (H reflex) is observed in a consistent and clearly identifiable way as a function of latency (35-45 ms). The electrical stimulus consists of the application of 1 square pulse (1 ms duration each pulse) every 10 seconds (10 pulses in total). The maximum intensity of the applied current will be according to the sensitivity and tolerance of the individual in both lower limbs during the tests on the sensory and motor nerves. The applied electrical pulse should not cause a painful sensation, but it can cause a tingling sensation. The test will be suspended if the individual reports pain or does not wish to continue with the research protocol. The "H" reflex test will be done in two parts. The first part of the protocol consists of determining the stimulus intensity vs. amplitude of motor responses from the appearance of the "M" wave and the "H" wave, for which the electric current will be increased in steps of 0.5 µA until the appearance of the waves. For this part, only one electrical pulse (1 ms duration) will be given every 10 seconds. The intensity of electrical current that will be used for the second part of the protocol will be that whose value in the amplitude curve of the H wave-electrical current intensity reaches 60% of the maximum amplitude. This stimulation value guarantees the reproducibility and minimum variability of this wave, which also prevents muscle contraction that contaminates the electrical register. The second part constitutes the paired electrical stimulation test in which two electrical pulses (1 ms in duration) will be produced at different frequencies between the pulses: 0.1, 1, 5 and 10 Hz. The interval between the paired pulses will be 10 s, until completing 10 series.
The electrophysiological recordings will be analyzed with the Clampfit 10.0 software. The latency and amplitude of the evoked potentials H1 and H2 will be determined for each electrical pulse and at all stimulation frequencies, taking the stimulus artifact as a reference. Subsequently, the ratio of the amplitude of the paired H2/H1 pulses will be determined to establish the modulation of spinal excitability. A ratio ≥0.6 for any stimulation frequency will be considered as an indicator of dysfunction in somatosensory processing according to Marshall et al.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intervention group | Experimental | Dietary Supplement: CocoaDiet for patients with diabetes + 4 capsules of cocoa powder, 500 mg each, daily for 12 weeks. |
| Control group | Placebo comparator | Other: PlaceboDiet for patients with diabetes + 4 capsules of methylcellulose 500 mg each, daily for 12 weeks. |
Who may qualify
- Ages
- 40 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Adults aged 40-60 years with a diagnosis of type 2 diabetes mellitus and diabetic neuropathy
- Minimum time of diagnosis of T2DM of 5 years
- Who have a Michigan Neuropathy Screening Instrument (MNSI) score ≥2
- Male and Female
- Have them sign the informed consent letter
Key exclusion criteria (2 listed)
- Subjects who modify their pharmacological treatment during the study
- Subjects who do not attend one of the intermediate consultations
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 |
|---|---|---|
| CocoaEach capsule of cocoa powder contains 12.5 mg of flavonoids, providing a total of 50 mg per day. | Dietary supplement | Intervention group |
| PlaceboEach capsule contains 500 mg of methylcellulose | Other | Control group |
Primary outcome
Toronto Clinical Scoring System (TCSS)
Time frame: At baseline and after 12 weeks
It is a system of clinical evaluations carried out by the researcher to identify peripheral neuropathy, assigning a score to symptomatology, reflexes and sensory tests. For the purposes of this study, the total score, i.e., the sum of all units on the scale, is reported. The minimum score that can be obtained is 0 points, while the maximum is 19 points. This means that the higher the score, the greater the severity (no grades were established based on the severity of the neuropathy). For the data represented in the row "Change from baseline at Week 12", it is the delta of the final measurement vs. the initial measurement, that is, the final measurement minus the baseline measurement.
17 secondary outcomes
Rate-dependent Depression of the H-reflex
Time frame: At baseline and after 12 weeks
BEST Questionnaire
Time frame: At baseline, after 4, 8 and 12 weeks
Bristol Stool Form Scale
Time frame: At baseline and 12 weeks
Weight
Time frame: At baseline, after 4, 8 and 12 weeks
Waist Circumference
Time frame: At baseline, after 4, 8 and 12 weeks
Waist-to-Height Ratio
Time frame: At baseline, after 4, 8 and 12 weeks
Abdominal Circumference
Time frame: At baseline, after 4, 8 and 12 weeks
Systolic Blood Pressure
Time frame: At baseline, after 4, 8 and 12 weeks
Diastolic Blood Pressure
Time frame: At baseline, after 4, 8 and 12 weeks
Glucose
Time frame: At baseline and after 12 weeks
Glycated Hemoglobin A1c
Time frame: At baseline and after 12 weeks
Triglycerides
Time frame: At baseline and after 12 weeks
High-density Lipoprotein Cholesterol
Time frame: At baseline and after 12 weeks
Triglycerides/HDL Ratio
Time frame: At baseline and after 12 weeks
Low-density Lipoprotein Cholesterol
Time frame: At baseline and after 12 weeks
Neutrophil/Lymphocyte Ratio
Time frame: At baseline and after 12 weeks
Diabetes 39 Instrument
Time frame: At baseline and after 12 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Diabetic Peripheral Neuropathy (DPN)
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. This study is not recruiting at the moment.
Carlos Cuéllar-Ramos, PhD study director
Anahuac University
Gabriela Gutiérrez-Salmeán, PhD study director
Anahuac University
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cocoa in people with Diabetic Neuropathies, run by Anahuac University at 3 sites in Mexico.
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 5 inclusion and 2 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: finished, as of the sponsor's last update on 1 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Mexico. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Toronto Clinical Scoring System (TCSS) (time frame: At baseline and after 12 weeks). 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 1 May 2025.