An open clinical observational study on the usefulness of 15 pre-defined homoeopathic medicines selected on the basis of repertorization of the symptoms and signs of Diabetic Distal Symmetrical Polyneuropathy (DDSP) and prescribed on the characteristic indications of the drug in single dose in a specific potency.
This is an analysis of the open clinical observational study conducted at Drug Standardisation Unit (H), Hyderabad. (Andhra Pradesh), under Central Council for Research in Homoeopathy (CCRH) from September 2006 to September 2009. 106 patients of type-2 diabetes mellitus (type-2 DM) suffering from DDSP were enrolled in the study and 95 patients completed the treatment and follow-up period of 12 months and were assessed using symptoms and signs assessment score (SSAS). 15 pre-defined medicines in centesimal scale of potencies (30, 200 and 1M) were prescribed. Allopathic medication (oral) was allowed for controlling diabetes in enrolled patients under the supervision of a Diabetologist.
The comparison of SSAS of DDSP at baseline and after 12 months by using Wilcoxon Sign Rank Test (WSRT) revealed statistically significant results (P=0.0001) after the prescription of trial homoeopathic medicines in 95 patients. In the course of observation there was substantial decrease in electro-diagnostic function, blood pressure, body weight, fasting and post-prandial blood sugar, slight decrease in HbA1C and micro albumin in urine. The dosage of allopathic medicine (oral) was kept unchanged during the treatment. Outcome assessment of 83 patients showed improvement in varying degrees viz markedly improved in 25 (26.31%), moderately in 46 (48.42%) and mild in 12 (12.13%). Lycopodium, Sulphur and Phosphorus are frequently indicated and were prescribed in 30, 200 and 1M potencies.
This is an observational study with positive results and needs further validation by suitable randomized controlled trial (s).
Observational study; diabetic distal symmetrical polyneuropathy; Characteristic indication; Lycopodium; Sulphur; Phosphorus; peripheral nerve conduction study
Diabetes mellitus (DM) is a metabolic disorder characterized by abnormal carbohydrate metabolism.1 DM increases the risk of arteriosclerosis and development of micro vascular and neurological complications. DDSP is a relatively early and most frequent common complication of DM.2-5 Theincidence of peripheral neuropathy (PN) is not known with any degree of certainty. It is reported to vary considerably (from 5% to more than 80%), mainly because the criteria for diagnosis and assessment have differed to a greater extent among the studies published so far. 6PN may be present in all patients with type-2 DM at any time after diagnosis and in patients with type – 1 DM after five years of DM. 9
The exact pathogenic mechanism of the development of PN is not fully understood and a number of observations and postulates have been described. The steady progression in severity is believed to be caused by metabolic abnormalities affecting the nerve tissue directly and / or indirectly via the supporting vasculation. 7-9 Additional causes like B1, B6, B12 deficiency are also postulated.10 Many epidemiological and prospective studies have shown both increasing patient’s age, duration of diabetes, hypertension (HT), obesity, smoking, hyperlipidemia and excessive consumption of alcohol may accelerate the development of DDSP.11-17
The literature indicates that the symptoms alone have relatively poor diagnostic accuracy in predicting the presence of DDSP. Signs are better predictors. Thus the combination of neuropathic symptoms, signs and electro- diagnostic findings (peripheral nerve conduction test) provide the most accurate diagnosis of DDSP. Frequently described symptoms are numbness, burning, pricking, lancinating, paresthesia and dysesthesia, and signs are abnormalities of primary senses (pain, touch, heat, cold, vibration, proprioception), the motor system – tendon reflex and electro-diagnostic studies which are a sensitive, specific validated measure of the presence of poly neuropathy. 18-26
Treatment of DDSP is multilayered, including etiology driven causal treatment, elimination of risk factor (obesity, smoking and excessive alcohol consumption and good glycemic control) and symptomatic therapy, as convincingly demonstrated by the diabetes control and complication trial (DCCT) studies. 27 Attempts have also been made by some practitioners and researchers with homoeopathic medicines and have produced positive resultin the management of DDSP. 28-29 From the review of literature, it appears that so far no significant work has been done in a scientific manner upholding the homoeopathic doctrine. There was a need to explore the efficacy of homoeopathic medicines, otherwise indicated for various diagnostic symptoms of DDSP. With this objective, the CCRH undertook this study with the aim to evolve a group of effective homoeopathic medicines in the management of DDSP, to deduce the indications of medicines and to provide a valuable data for indexing various homoeopathic repertories.
To evolve a group of efficacious homoeopathic medicines in the management of DDSP, out of 15 pre-defined homoeopathic trial medicines, by observing the hypothesis “use of homoeopathic medicines selected on the basis of repertorisation of symptoms and signs of the disease DDSP and prescribed on characteristic indications of the drug in single dose in specific potency, is effective in relieving the patients suffering from DDSP”.
1. To determine and verify characteristic symptoms of medicines used.
2. To check the progress of the disease and
3. The following clinical findings will also be considered in the study
a) Control of blood sugar levels.
b) Change in symptoms and signs of neuropathy.
c) Change in the symptoms and signs of occlusive arterial disease
Material and methods:
An open, prospective and observational clinical trial was conducted from September 2006 to September 2009 at Drug Standardisation Unit (H), Hyderabad. The patients were enrolled from the OPD after confirmation of the diagnosis and conformed to inclusive criteria as per protocol under the supervision of an endocrinologist appointed by the Council. The protocol was approved by an ethical committee. Before administrating any test, aims and methodology of the research were explained to all patients, who were then asked to sign a written informed consent sheet. Patients’ symptoms and signs were quantified on 14 symptoms and signs of DDSP known as SSAS, which is developed by the council (Table-I)
Inclusive and exclusive criteria:
Patients enrolled were type-2 DM with Hb A1C less than 8.0% and of both sexes, age ranging from 32 to 74 (table.1) years presenting with illness from 3 months to 25 years duration (table.4) with symptoms and signs like numbness, burning, pricking, lancinating, paresthesia , dysesthesia,: primary sensory abnormalities of (pain, touch, heat, cold, vibration, proprioception), tendon reflex and supported by electro-diagnostic studies (peripheral nerve conduction test). The patients who were on allopathic treatment for maintaining blood sugar level were advised to continue under the diabetologist’s supervision. Patients suffering from diabetic mononeuropathy, polyradiculopathy, amyotrophy, autoneuropathy, abnormalities of gait, development of typical charcot joint particularly in the feet, loss of arch with multiple fractures of the tarsal bones, absence of stretch reflexes, wrist drop, foot drop, paralysis of III, IV or VI cranial nerves, myocardial infarction, any neuropathy due to other causes and Hb.A1C above 8.0% were excluded from the study.
Selection of trial medicine:
15 pre-defined trial medicines were selected by repertorising the diagnostic symptoms and signs of the DDSP and the rubrics taken were viz. Diabetes mellitus; numbness, foot; skin, formication; senses, delusions of; skin, pricking; senses, hyper acute; painlessness of complaints usually painful; pain, nerves along; pain, rest, aggr; pain, tingling; burning, foot, sole; pain, stitching; pain, night;. The repertorisation was done using the complete repertory in CARA professional. 15 medicines which covered 3rd grade were considered. These are Sulphur, Lycopodium, Rhux.tox., Nux vomica, Phosphoric acid, Phosphorus, Arsenicum album, Conium. mac, Cocculus, Opium, Secale cor, Rhododendron, Platinum, Graphites and Stramonium. On the basis of the totality of the symptoms of each patient the simillimum was selected out of these 15 pre-defined homoeopathic medicines and prescribed in centesimal potency (30). Materia medica was referred for final selection of the simillimum.
8 pre-defined trial medicines were selected by repertorising the rubrics of the acute phase with pain i.e., pain, neuralgic nerve along; pain, general rest, aggr; pain, general, tingling; pain, extremities, burning, foot, sole; pain, extremities, stitching; pain extremities, night The repertorisation was done using the complete repertory in CARA professional. 8 medicines which covered 3rd grade were considered. These are Chamomilla, Calcarea carb, Kali carb, Lycopodium, Mercurious, Rhus.tox, Sulphur and Plumbum met. On the basis of the totality of the symptoms of each patient, the indicated medicine is selected from these 8 pre-defined acute medicines and prescribed in 6c. Materia medica was referred for final selection of the indicated drug.
Treatment and follow up schedule:
The first prescription from 15 pre-defined medicines was based on repertorisation of the presenting symptoms and signs of the disease guided by characteristic, particular, mental/ emotional and physical attributes of the patients. Medicines were prescribed in centesimal scale of potency starting with single dose of 30 potency, 4 globules of size 30 followed by placebo from next day onwards, three times a day for two weeks. Follow-up was provided weekly for first month, fortnightly for the next two months and monthly visits onwards up to 9th month. Repetitions of indicated medicines were done depending on the intensity of the symptoms. 200 and 1M potencies were prescribed subsequently after the 30 acted but did not relieve clinically. Change of prescription was allowed only twice for each patient.
In acute exacerbation of chronic disease in the follow-up, acute medicine was selected depending on the totality of acute pain symptoms from 8 pre-defined medicines and prescribed in 6c. Repetition in same potency (6c) is made depending upon the need. Change of medicine is considered when there is no desirable improvement from 8 pre-defined drugs of acute phase and repetition is done in the same way as was followed in first prescription. Life-style management, like advising diabetic self care, dietary schedule, care of feet and prevention of injuries, precaution while cutting nails and appropriate advice on alcohol or tobacco abuse/ addiction and regularly needed exercises were given to the patients.
Out- come assessment:
Assessment was done either after all the potencies (30, 200 and 1M) of the trial drug had been used, or after a lapse of a term of 3 months from enrollment of the patient, whichever is earlier. Patients clinically improved were discontinued from therapy and put on periodical observation for a symptom free period till one year from the enrollment. Those who had not improved were given a change in therapy; following the same guidelines as per the selection of the first prescription, and that case was taken as a new drug trial case in the study. Primary outcome measure was reduction in SSAS. Improvement was calculated using the formula = Baseline score – Score at end/baseline scoreX100. Changes thereupon were graded as markedly (> 75%), moderately (50 to <75%), mild (25 to <50%), not significant (<25%), static (No change) and worse (Increase in symptom score).
95 patients who completed their follow-up of one year were included in the data analysis. The characteristics of age and sex of the patient are included in the study and reported in table-2. There was a significantly increased prevalence of DDSP in increasing age from 30.52% in the < 50 years age group to 69.47% in the ? 70 years age group. In all, 50 male cases (52.63%) and 45 female cases (47.37%) were studied. This reveals a prevalence rate greater in men. The prevalence of DDSP is related to duration of diabetes and was present in 24.21% of patients with diabetic duration of < than 5 years and 75.79% of those with diabetic duration ? 25 years (table-3). 85 cases (89.47%) with < 5 years of DDSP complaints were observed in the study (table.4).
Several risk factors like HT (26) showed improvement in 10 cases (38.46%), obesity (13) showed decrease in 2 cases (mean body mass index is 26.35, SD=3.75) (Table-5), smoking (5), excessive consumption of alcohol (3), increased micro albumin in the urine (26) and improved in 6 cases (23%). Hereditary (8) and prolonged hyper glycemia (72, >5 years) were identified and assessed. Four patients withdrawn from B-Complex medicine during treatment and have shown improvement in PN symptoms with Sulphur and Lycopodium (30,200,1M) in two cases each.
The hypothesis “use of homoeopathic medicines selected on the basis of repertorisation of symptoms and signs of the disease DDSP and prescribed on characteristic indications of the drug in single dose in specific potency, is effective in relieving the patients suffering from DDSP”… is proved in our study and assessed in terms of symptoms, signs and diagnostic parameters through SSAS (table-1), and involved five efficacious medicines from the 15 pre defined trial medicines in the management of DDSP. At the baseline, the patients most commonly experienced Bilateral/ symmetric distal sensory loss (72 ), Paresthesia (91), Dysesthesia (04), Numbness, tingling, that begins in the feet and spreads proximally (74), then burning in the feet and spreads proximally (71), Lancinating or lightning pain in the lower extremities (84 ), “Glove and stocking” sensation in the extremities (08), diminished superficial pain (57), exaggerated superficial pain (21), diminished perception of vibration (56), diminished perception of temperature (58), diminished perception of position (23) tendon reflexes diminished or absent (11), nerve conduction test sensory, slow (38), Nerve conduction test motor, reduced (25). Scores at baseline and at the end of the 12th month (frequency of cases and % of total) show significant decrease in the symptoms and signs after homoeopathic treatment excepting in dysesthesia and tendon reflexes (diminished) (Table-6). This improvement also is statistically significant (p=0.0001) (Table-7&8).
The studies on the electrical conduction of the nerves are reported in table-9. There is varying difference in improvement in distal motor latency (DML), compound muscle action potential (CMAP) and motor nerve conduction velocity (MNCV) of tibial and common peronial nerve, and also in distal sensory latency (DSL) sensory nerve action potential (SNAP) and sural nerve conduction velocity (SNCV) of sural nerve. Over the period of one year observation, the results obtained reveal 4 cases improved in sensory and 8 cases in motor conduction and p value is 0.046 and 0.005 respectively, which is statistically significant (Table-7).
Intensity of DDSP was assessed according to score. One year’s observation revealed that 51 moderate cases (53.68%) at baseline have turned to mild after treatment. (Table -10). On completion of the study, outcome assessment showed 25 markedly improved, 46 moderately, 12 mildly, no significant improvement in 8 and 4 not improved (Table-11).
Out of 15 pre-defined medicines, only 5 medicines were involved and prescribed viz. Lycopodium in 43 (30,200, 1M), Sulphur in 33 (30,200, 1M), Phosphorus in 17 (30,200, 1M), Acid.Phos in 01 (30,200), and ArsenicumAlb in 01 case (30,200, 1M) and percentage improvement observed is 84.55%, 100%, 70.58%, 100% and 100% respectively. The details are given in table- 11.
Acute exacerbation of chronic disease was observed in 41 cases during follow-up. Out of 8 pre-defined acute phase medicines, 4 drugs were prescribed in 6c viz. Lycopodium, Rhus.tox, Sulphur and Plumbum met and improvement was observed in 87.5%, 80%, 93.75% and 75% respectively (Table-12). In our study repetition was done as and when required (3 times per day) till the acute pain symptoms were reduced.
The characteristic indications of the 5 drugs found effective in our study was determined when selecting the drug and verified during trial (table-13). Neuropathic ulceration is a complication of DDSP that occurs predominantly in individuals with loss of protective sensation. In our study such progress of disease has not occurred. DDSP can significantly impact an individual’s quality of life and daily activities by causing major disturbance in sleep, mood changes and impairment of social, occupational and recreational function. In our study, life-style management has shown significant improvement. Autonomic dysfunction is also established in the progress of the disease. In our study it is observed that 10 cases having hypertension were improved by Lyco 30, 200,1M (6) and Sulphur 30, 200, (4); abnormal sweating in 3 cases were better from Sulphur 30, 200, 1M and impotency in 2 cases was ameliorated by Lyco 30, 200,1M. This shows clearly that the check of progress of disease complications is maintained by prescribed drugs, thus fulfilling part of the secondary objective.
In the present study it is observed that the laboratory findings showed statistically significant decrease in FBS (p=0.0001), PPBS (p=0.0001) and HbA1C (p=0.006) (table-15). This shows that glycemic control is a factor for improving neurological problems of DDSP patients. The dosage of oral allopathic medication for controlling diabetes was kept unchanged during the treatment.Thus, effective control of blood sugar level is also fulfilled in our study.
The symptoms and signs of neuropathy were found to be significantly improved both symptomatically and statistically p=0.0001 (table- 6-8). Certain occlusive arterial disorders were observed in a few patients and it was assessed. Mild pain while walking (claudication) in 4 cases, severe pain when walking relatively at shorter intervals (intermittent claudication), in 8 cases pain while at rest (leg pain) in 7 cases and found improved in 2 cases (50%), 6 cases (75%), 3 cases (42.85%) respectively with the prescribed medicines (table-14), thus fulfilling the protocol study.
A group of 15 pre-defined trial homoeopathic medicines were used in the management of patients suffering from DDSP. 95 patients were followed-up and completed the treatment. DDSP is a relatively early and most frequent and common complication of DM (Pirart.J) 3. This is proved in our study. In <15 years of diabetic history, DDSP was observed in 78 cases (82%) (table-3). Out of 362 screened cases of DM having neuropathic problems 247 cases (68.23%) had DDSP (141 Hb.A1C>8% and 106 Hb.A1C<8%) (Fig.1). There was a significantly increase prevalence of PN in increasing age 30.52% in the <50 years age to 69.47% in the ? 70 years age group. This signifies findings of Tesfaye S et al.11 PN may be present in all patients with type-2 DM at any time after diagnosis, (Greene. D.A et al) 9 but our study showed that it is more prominent in the patients of DM more than 5 years (75.78%) of duration (table.3). The prevalence of PN is related to the duration of diabetes. Pirart. J 3 reported a prevalence of 50% among patients who have had diabetes for 25 years. In another study Partanen J et al 14 reported a prevalence of 41.9% among diabetic patients of 10 years duration. The present study shows 24.2% in the patients with diabetic duration < 5 years to 75.79% in those with ? 25 years (table-3). This variation is due to the criteria for diagnosis and assessment has deferred to a greater extent in the studies conducted so far (Spefania Lelli, et al)6 (Master.RF. et al). 13
Men suffer more than women which is observed in epidemiological study conducted so far (Tesfaye. S et al)11. This is proved in our study. Poor metabolic control and increase prevalence and severity of PN was stated by Klein R et al 16 and Tackmann W et al. 26 the same was not confirmed by Mohsen Jenghordani et al4. In our study 141 patients had HbA1C more than 8% and were excluded from our study (fig.1). All of them had marked severe PN symptoms. This confirms the former studies. Prolonged hyperglycemic exposure is considered to be the cause for the development of PN as stated by Tesfaye. S et al.11 In the present study 72 patients (75.78%) having diabetes with duration ranging from 5 years to 25 years showed the causative factor for DDSP (table 3). Smoking is related to the prevalence of PN as confirmed by Tesfaye. S et al, but Mohsen Jenghordani et al4 showed no significant effect. The present study showed improvement in the PN symptoms in all the 5 patients who had stopped smoking. In our study 10 cases had improved in hypertension, 2 cases improved in hyperlipidemia by prescribed drugs along with the neuropathic symptoms and signs. Thus consistent with prior studies (Lehtinen J. M, et al)7, present study was able to find association with PN. Proteinuria is found to be a risk factor for PN (Int.J Diabetes.Metab.14:126-133, 2006). This is confirmed in our study. 6 cases have improved in increase micro albumin in urine during our study. Gorson. K.C. and Ropper. A.H has postulated B1, B6 as to the cause for PN. In our study 4 patients taking B1, B6, and B12 were advised to stop during the course of the treatment and have improved through indicated homoeopathic medicine. This proves the association of the deficiency rather than cause. Thus the long term goal in diabetic PN includes elimination of risk factors such as obesity, smoking, excessive alcohol consumption, good glycemic control as convincingly demonstrated by DCCT27 studies, and this is verified in our study. The criteria for diagnosis of DDSP are abnormalities in two of three areas: sign, symptoms and electro diagnostic study (Fagerberg S E)23 and this is followed in our study. As signs and symptoms are unique to each individual in respect of intensity, extension and modifying factors hence SSAS is designed accordingly and evaluated (table-1).
The primary object relates to the evaluation of a group of efficacious homoeopathic medicines from 15 pre-defined trial medicines by observing the hypothesis “use of homoeopathic medicine selected on the basis of repertorisation of symptoms and signs of the disease DDSP and prescribed on characteristic indication of the drug in single dose in specific potency is effective in relieving the patients suffering from DDSP”. It is verified in our study (table-6, 9,10,11) and proved statistically significant (p=0.0001) (table-7,8,9). The trial medicines found useful in this study are Lycopodium, Sulphur, Phosphorus, Arsenicumalbum and Acid.phos, which are similar to those used in previous studies(Guillermo.Z) 28 (Pomposelli.R, et al). 29
In §73, Hahnemann stated that certain individuals with chronic illness experience recurrent acute ailments due to flare-up of latent psora. This is observed in our study, i.e acute phase with pain symptoms. Kent advocated treating such acute exacerbations as and when they reappeared in the course of treatment, without disturbing the plan of treatment of chronic illness. This is also observed in our study. Thus in our study, acute exacerbation of the chronic state during the course of treatment was effectively controled through 4 out of 8 pre-defined acute drugs viz Lycopodiun 6, Plumbum met 6, Rhus.tox 6, and Sulphur 6 (table-12). These drugs were also used in early studies28, 29 but not as acute drugs as used in present study.
According to the homoeopathic method, the objective of the treatment is the whole person and only secondarily the treatment of the disease at an organic level 31. In our study, the objective is selecting the prescribed medicine on the basis of characteristic symptoms from the 15 pre-defined drugs by upholding the law of Simillimum. Thus characteristic symptoms of the prescribed drugs are determined and verified (table-13).
A check on the progress of disease complications is maintained by prescribed drugs and management throughout the study. That HbA1C is not associated with PN, was found by Tackmann.W et al26. But other studies have yielding evidence of association (Pirart.J)3. The present study reveals the improvement in FBS in 72(75.78%) (p=0.0001), PLBS in 71 (74.75%) (p=0.0001) and HbA1C in 35 (36.84%) (p=0.006). There is significant improvement in symptoms and signs of PN in our study (p=0.0001) in spite HbA1C not improved that significantly, which reveals less association. DDSP is a tubercular miasm (psora and syphilis) for which drugs like Sulphur, Phosphorus, Lycopodium, Arsenicum album and Acid phos are indicated. Hence the miasmatic approach in the study is upheld. During the course of the treatment there was reduction in associated symptoms (table-14), prior to maximum improvement in the DDSP symptoms and signs by the prescribed homoeopathic medicines. This verifies Hering’s law of cure i.e. symptoms disappear above downwards; centre to periphery; from more important to less important organ (fig.2) and further it also verifies the reverse order of cure, i.e glycemic state is the cause of DDSP. On careful observation during the treatment, the DDSP symptoms and signs have improved significantly (p=0.0001) (table-6), then glycemic state (HbA1C) (p=0.006) (table-8) i.e reverse order of the chronological onset of the symptoms (fig.3).
DDSP poses a formidable threat to the diabetes patient, and early and comprehensive neurological investigations and treatment is warranted. Thus the present study proves homoeopathic management is effective, gentle, safe and cost effective for diabetic patients with PN. As the study did not have any control group, randomization and blinding, it cannot be concluded that homoeopathic therapy is effective in DDSP patients among the Indians. Hence CCRH has already taken an initiation for commencing randomized control trials in this disorder.
This is an observational study with positive results and needs further validation by suitable randomized control trial(s).
The author is grateful to