Laser Acupuncture on Diabetes-induced Peripheral Neuropathy

This prospective, randomized, single-center, parallel-group study will be cooperatively conducted in the neurology and traditional Chinese medicine department of Tainan Municipal An-Nan Hospital, China Medical University in Tainan, Taiwan. Study approval will be applied from the TMANH Research Ethics Committee. After screening eligibility and completing baseline assessments, we obtained informed consent from all patients before enrollment. Participants were randomized to either the laser acupuncture, the sham laser acupuncture group using a block randomization method with allocation ratio of 1:1(Figure 7). Before study commencement, the statistician created a randomization sequence using IBM® SPSS® Statistics and contained it in sealed envelopes. The balanced sample size was ensured by dividing the participants into blocks of two. All eligible participants and assessors were unaware of the assignment order. Both the physician and participants will be unaware of the group allocation. Participants were allowed to withdraw from the study at any time.

• Patient eligibility

We included the patients with the following inclusion criteria(Dietzel, et al. 2021):

1. female or male patients (aged over 18 years) with diabetes mellitus type II.

2. patients have symptoms (numbness, tingling, burning, stabbing, shooting pain, etc.) and signs (symmetric decreased distal sensation, or decreased or absent ankle reflexes) of diabetic neuropathy.

3. presence of abnormal nerve conduction study, or presence of neuropathy is likely tested by Semmes-Weinstein 10-g monofilament, or decreased vibration sensation tested by 128Hz vibration tuning fork

4. patients who have completed titration of pain medication or stopped accepting physical therapy against DPN;

5. must provide written informed consent.

The main exclusion criteria for the patients are as follows:

1. severe DPN with muscular weakness of the proximal leg muscles;

2. neuropathy due to other reasons (such as HIVD, malignancy, severe renal disease, hepatitis, thyroid disease, vitamine B12 deficiency, virus infection (such as: human immunodeficiency virus infection, etc), syphilis, alcohol, neurotoxic drug use, inflammatory disease (such as chronic inflammatory demyelinating polyneuropathy), heavy metal intoxication, hereditary disease, etc)

3. severe peripheral artery disease in Fontaine stage IV(Focal tissue necrosis, ulceration or gangrene);

4. traumatic lesions of the nerves or vessels in the lower extremities;

5. opioid use before inclusion in the study;

6. regular use of cannabis or cannabinoids;

7. severe mental illness;

8. severe impairment of cognitive function;

9. pregnancy or lactation

10. obesity (BMI>35 kg/m2); • Randomization and Intervention After screening for inclusion/exclusion criteria, eligible participants signed the written informed consent and completed the baseline assessments that included a quantitative sensory test using the SWM and patient-reported outcome measurements, and the nerve conduction study. Eligible participants completed the baseline assessments within seven days before the interventions.

According to the previous randomization assignment, each patient will be assigned to 2 groups: (1) the laser acupuncture group and (2) the sham laser acupuncture group. Only the statistician aware of the randomized order for each participant. Each participant will receive 24 interventions within 8 weeks, including three interventions per week for 8 weeks. The selected acupoints for laser acupuncture and electro-acupuncture were the same real acupoints, including bilateral LI 4, PC6, LI11, GB 34, ST 36, SP 6, KI 3, LR 3。

• Statistical analysis All data will be analyzed using IBM® SPSS® Statistics version 22 (Statistical Product and Service Solutions Statistics, I.B.M., Inc., Armonk, NY, USA). For demographic data, continuous data will be analyzed using a two-sample t-test or Mann-Whitney U test, while categorical data will be analyzed using Fisher's exact test. If the data of each group fail to pass the Shapiro-Wilk normal distribution test (all p value < 0.05), the between-group differences will be examined using the nonparametric Mann-Whitney U test, and the intra-group differences will be examined using the Wilcoxon signed-rank test. If the measurements of the baseline values will be as per the Shapiro-Wilk normal distribution test (all p value > 0.05), the difference between groups will be examined using a two-sample t-test, and the intra-group difference was examined using a paired t-test. Differences between or within groups were considered significant at p < 0.05.