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Efficacy of γ-linolenic Acid and Thioctic Acid in Patients With Diabetic Neuropathy

Primary Purpose

Diabetic Neuropathy

Status

Completed

Phase

Phase 4

Locations

Korea, Republic of

Study Type

Interventional

Intervention

γ-linoleic acid and placebo(Thioctic Acid)

Thioctic Acid and placebo(γ-linoleic acid)

About this trial

This is an interventional prevention trial for Diabetic Neuropathy

Eligibility Criteria

20 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patients who were between 20 years and 75 years at screening
Patients who were diagnosed with type 2 diabetes and whose HbA1c levels were less than 11% at screening
Patients with a score of 4 or more on the Visual Analogue Score(VAS)
One or more of the following items
- If the physical examination score of the Michigan Neuropathy Screening Instrument Score (MNSI) is more than 2 points at the initial screening
- type 2 diabetic patient who complained one or more of pain, burning sensation, numbness, and sensory loss and measured the current perception threshold (CPT) of the peroneal nerve at three frequencies (2000Hz, 250Hz, 5Hz) Anyone whose diabetes mellitus has been diagnosed as diabetic neuropathy
Patients who decided to voluntarily participate in clinical trials and agreed in writing

Exclusion Criteria:

Peripheral neuropathy caused by other causes other than diabetes
Those are suffering from other painful conditions that are so severe that diabetic neuropathy can not be assessed
If you have a progressive or degenerative neurological disorder
Patients with a systolic blood pressure(SBP)≥ 160 mmHg or ≤ 100 mmHg or a diastolic blood pressure(DBP) ≥ 95 mmHg or ≤ 60 mmHg
Patients who were positive for human immunodeficiency virus (HIV), hepatitis B (HBV), or hepatitis C (HCV) test
patients with liver dysfunction (ALT / AST> 3 times the upper limit of normal)
Patients with renal dysfunction (Serum creatine> 2.0 mg / dl)
Patients with thyroid dysfunction (Thyroid and anti-thyroid medications may be included in this study if they are maintained in normal state.)
Patients with amputation (including toes) or infections of the lower extremities
The following diseases are clinically significant patients
- Unstable coronary artery disease or peripheral vascular disease
- Liver, kidney, lung, hematologic disease
- Cancer (within 5 years if possible)
Patients who have suicide attempts or suicidal tendencies and who have a psychiatric history within 6 months before starting the trial
Patients with substance abuse or chronic alcohol abuse within 2 years prior to taking the test
Patients who received intravenous steroid injection or topical anesthetic injection within 2 months before participating in the study
Patients who participated in other studies within 4 weeks before participating in the trial, or who are currently taking medication for other research
Screening After randomization for 2 weeks (pause period) before screening, antipsychotics, antipsychotics, sleep depressants, antidepressants, antiepileptics, muscle relaxants, analgesics (narcotic analgesics, NSAIDs, tramadol etc.) Patients who received capsaicin or who received percutaneous electrical nerve stimulation therapy (TENS) or acupuncture
Patients with a history of hypersensitivity or clinically significant hypersensitivity reactions to this drug substance and soybean oil, soy or peanut
Patients with clinically significant skin disease or severe skin irritability
Pregnant or lactating women
patients suffering from schizophrenia or those who are treated with chloropromazine, mesoridazine, thioridazine, fluphenazine, perphenazine, trifluoperazine, haloperidol (haloperidol), loxapine (loxapine) and other drugs known to cause epileptic seizures
In addition to the above items, patients who are deemed inappropriate by clinical trial researchers

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Test group

Control Group

Arm Description

γ-linoleic acid (Evoprim soft capsule) twice a day and 4 capsules at a time. Thioctic Acid(LipoA HR Tab. 600mg) placebo once a day and 1 tablet at a time.

Thioctic Acid(LipoA HR Tab. 600mg) once a day and 1 tablet at a time. γ-linoleic acid (Evoprim soft capsule) placebo twice a day and 4 capsules at a time.

Outcomes

Primary Outcome Measures

Changes of Visual Analog Scale(VAS)

The Visual Analog Scale(VAS) score is 0 point for no symptom, 10 points for the most severe symptom, and the patient is asked to mark the degree of subjective pain symptoms as an integer.

Changes of Total Symptom Score(TSS)

Total Symptom Score(TSS) classifies diabetic neuropathy symptoms into four categories (pain, burning pain, paresthesia, numbness). The frequency (Occasional, Frequent, Continuous) and symptom intensity (Absent, Slight, Moderate, Severe) are calculated through each question and the score is obtained according to the visual analog scale. It is calculated from 0 point up to 14.64 points.

Secondary Outcome Measures

Changes of Michigan Neuropathy Screening Instrument(MNSIQ)

A 15-item questionnaire (MNSIQ) is used to assess deformation, infection, skin thickening of the skin's stratum corneum, and ulcers. MNSIQ was designed to screen for diabetic neuropathy through questionnaires on 15 questions that are related to neuropathic symptoms (pain, temperature, and sensation). Two of 15 (number 4 and 10) are vascular symptoms and are excluded from the total score regardless of the results. If you answered 'No' to questions 7 and 13, you will get 1 point. In the end, scores ranging from 0 to 13 indicate that the higher the score, the more severe the neuropathic symptoms.

Changes of Michigan Neuropathy Screening Instrument(MNSIE)

A foot test (MNSIE) is used to assess deformation, infection, skin thickening of the skin's stratum corneum, and ulcers. MNSIE evaluates foot shape, foot ulceration, ankle reflex, sense of vibration of big toe, monofilament right and left. The score ranges from point 0 to 10, and when the score is above 2, it is diagnosed as neuropathy.

Changes of Current perception Threshold(CPT)

Sensory nerve conduction threshold (SNCT) is a unique method for evaluating all three sensory neurons (small unmyelinated fibers, small myelinated fibers, and large myelinated fibers) that make up more than 90% of sensory nerves. It seems to be possible to objectively evaluate sensory nerve of small fiber which recovered early in diabetic neuropathy(Using neurometer).

Changes of Modified Brief Pain Inventory-diabetic polyneuropathy(Modified BPI-DPN)

Modified Brief Pain Inventory-diabetic polyneuropathy(Modified BPI-DPN) displays the pain area on the human figure, the number of pain sites, treatment of pain, and pain medication. Pain severity refers to the pain sensation- identification aspect (pain threshold). The worst pain, the least pain, the pain average, and the pain now for the last 24 hours are displayed on the 10-point scale (0 points: none, ~ 10 Point: too big to imagine). Pain interference is the emotional-synchronous aspect of pain (pain tolerance). It classifies general activity, mood, walking, working, relationship, sleep and enjoyment of life, and use the 10-point scale (0 points: none to 10 points: completely disturbed).

Changes of EuroQol-5 Dimensions(EQ 5D)

EQ-5D index = 1 - (0.050 + 0.096 M2 + 0.418 x M3 + 0.046 x SC2 + 0.13 x SC3 + 0.051 x UA2 + 0.028 x UA3 + 0.037 x PD2 + 0.151 x PD3 + 0.043 x AD2 + 0.158 x AD3 + 0.050 × N3) - 1 if the variable is applicable, 0 if not (M: mobility, SC: self-care, UA: usual activity,, PD: pain / discomfort, AD: anxiety / depression) * Variable definition M2: 1 if mobility is 'level 2', 0 if not M3: 1 if mobility is 'level 3', 0 if not SC2: 1 if self-care is 'level 2', 0 if not SC3: 1 if self-care is 'level 3', 0 if not UA2: 1 if usual activity is 'level 2', 0 if not UA3: 1 if usual activity is 'level 3', 0 if not PD2: 1 if pain / discomfort is 'level 2', 0 if not PD3: 1 if pain / discomfort is 'level 3', 0 if not AD2: 1 if anxiety / depression is 'level 2', 0 if not AD3: 1 if anxiety / depression is 'level 3', 0 if not N3: 1 if there is at least one level 3, others are 0

Full Information

NCT ID

NCT03914404

First Posted

April 10, 2019

Last Updated

April 11, 2019

Sponsor

Chonbuk National University Hospital

1. Study Identification

Unique Protocol Identification Number

NCT03914404

Brief Title

Efficacy of γ-linolenic Acid and Thioctic Acid in Patients With Diabetic Neuropathy

Official Title

A 12-week, Multi-center, Randomized, Double-blind, Double Dummy, Parallel Clinical Trial to Compare the Efficacy of γ-linolenic Acid and Thioctic Acid in Patients With Diabetic Neuropathy

Study Type

Interventional

2. Study Status

Record Verification Date

April 2019

Overall Recruitment Status

Completed

Study Start Date

January 26, 2016 (Actual)

Primary Completion Date

March 30, 2016 (Actual)

Study Completion Date

July 25, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Chonbuk National University Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This study was a 12-week, multi-center, randomized, double-blind, double dummy, parallel clinical trial to compare the efficacy of γ-linolenic acid and Thioctic acid in patients with diabetic neuropathy.

Detailed Description

This study evaluated non-inferiority about the efficacy and safety of γ-linolenic acid (Evoprim soft capsule) through patients with diabetic neuropathy were compared γ-linolenic acid (Evoprim soft capsule) and Thioctic acid(LipoA HR Tab. 600mg) using double-blind, double dummy clinical trials. First outcome measures are Visual Analog Scale(VAS) and Total Symptom Score(TSS), secondary outcome measures are Michigan Neuropathy Screening Instrument(MNSI), Current perception Threshold(CPT), Modified Brief Pain Inventory-diabetic polyneuropathy(Modified BPI-DPN) and EuroQol-5 Dimensions(EQ 5D).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Diabetic Neuropathy

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

100 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Test group

Arm Type

Experimental

Arm Description

γ-linoleic acid (Evoprim soft capsule) twice a day and 4 capsules at a time. Thioctic Acid(LipoA HR Tab. 600mg) placebo once a day and 1 tablet at a time.

Arm Title

Control Group

Arm Type

Experimental

Arm Description

Thioctic Acid(LipoA HR Tab. 600mg) once a day and 1 tablet at a time. γ-linoleic acid (Evoprim soft capsule) placebo twice a day and 4 capsules at a time.

Intervention Type

Drug

Intervention Name(s)

γ-linoleic acid and placebo(Thioctic Acid)

Intervention Description

γ-linoleic acid (Evoprim soft capsule) twice a day and 4 capsules at a time. Thioctic Acid(LipoA HR Tab. 600mg) placebo once a day and 1 tablet at a time.

Intervention Type

Drug

Intervention Name(s)

Thioctic Acid and placebo(γ-linoleic acid)

Intervention Description

Thioctic Acid(LipoA HR Tab. 600mg) once a day and 1 tablet at a time. γ-linoleic acid (Evoprim soft capsule) placebo twice a day and 4 capsules at a time.

Primary Outcome Measure Information:

Title

Changes of Visual Analog Scale(VAS)

Description

The Visual Analog Scale(VAS) score is 0 point for no symptom, 10 points for the most severe symptom, and the patient is asked to mark the degree of subjective pain symptoms as an integer.

Time Frame

12 weeks

Title

Changes of Total Symptom Score(TSS)

Description

Time Frame

12 weeks

Secondary Outcome Measure Information:

Title

Changes of Michigan Neuropathy Screening Instrument(MNSIQ)

Description

Time Frame

12 weeks

Title

Changes of Michigan Neuropathy Screening Instrument(MNSIE)

Description

Time Frame

12 weeks

Title

Changes of Current perception Threshold(CPT)

Description

Time Frame

12 weeks

Title

Changes of Modified Brief Pain Inventory-diabetic polyneuropathy(Modified BPI-DPN)

Description

Time Frame

12 weeks

Title

Changes of EuroQol-5 Dimensions(EQ 5D)

Description

Time Frame

12 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patients who were between 20 years and 75 years at screening Patients who were diagnosed with type 2 diabetes and whose HbA1c levels were less than 11% at screening Patients with a score of 4 or more on the Visual Analogue Score(VAS) One or more of the following items If the physical examination score of the Michigan Neuropathy Screening Instrument Score (MNSI) is more than 2 points at the initial screening type 2 diabetic patient who complained one or more of pain, burning sensation, numbness, and sensory loss and measured the current perception threshold (CPT) of the peroneal nerve at three frequencies (2000Hz, 250Hz, 5Hz) Anyone whose diabetes mellitus has been diagnosed as diabetic neuropathy Patients who decided to voluntarily participate in clinical trials and agreed in writing Exclusion Criteria: Peripheral neuropathy caused by other causes other than diabetes Those are suffering from other painful conditions that are so severe that diabetic neuropathy can not be assessed If you have a progressive or degenerative neurological disorder Patients with a systolic blood pressure(SBP)≥ 160 mmHg or ≤ 100 mmHg or a diastolic blood pressure(DBP) ≥ 95 mmHg or ≤ 60 mmHg Patients who were positive for human immunodeficiency virus (HIV), hepatitis B (HBV), or hepatitis C (HCV) test patients with liver dysfunction (ALT / AST> 3 times the upper limit of normal) Patients with renal dysfunction (Serum creatine> 2.0 mg / dl) Patients with thyroid dysfunction (Thyroid and anti-thyroid medications may be included in this study if they are maintained in normal state.) Patients with amputation (including toes) or infections of the lower extremities The following diseases are clinically significant patients Unstable coronary artery disease or peripheral vascular disease Liver, kidney, lung, hematologic disease Cancer (within 5 years if possible) Patients who have suicide attempts or suicidal tendencies and who have a psychiatric history within 6 months before starting the trial Patients with substance abuse or chronic alcohol abuse within 2 years prior to taking the test Patients who received intravenous steroid injection or topical anesthetic injection within 2 months before participating in the study Patients who participated in other studies within 4 weeks before participating in the trial, or who are currently taking medication for other research Screening After randomization for 2 weeks (pause period) before screening, antipsychotics, antipsychotics, sleep depressants, antidepressants, antiepileptics, muscle relaxants, analgesics (narcotic analgesics, NSAIDs, tramadol etc.) Patients who received capsaicin or who received percutaneous electrical nerve stimulation therapy (TENS) or acupuncture Patients with a history of hypersensitivity or clinically significant hypersensitivity reactions to this drug substance and soybean oil, soy or peanut Patients with clinically significant skin disease or severe skin irritability Pregnant or lactating women patients suffering from schizophrenia or those who are treated with chloropromazine, mesoridazine, thioridazine, fluphenazine, perphenazine, trifluoperazine, haloperidol (haloperidol), loxapine (loxapine) and other drugs known to cause epileptic seizures In addition to the above items, patients who are deemed inappropriate by clinical trial researchers

Overall Study Officials: