A Randomized,Active-Controlled,Assessor-Blinded,Parallel Group Clinical Study to evaluate the safety and efficacy of Asgand and Brahmi in the Management of Qillat-e-Darqiyyat Asli (Primary Hypothyroidism)

Need for the Study

Primary hypothyroidism refers to hormone deficiency caused by intrinsic thyroid gland dysfunction that disrupts the synthesis and secretion of T4 and T3. Primary hypothyroidism is one of the most common endocrine conditions, occurring in 5% of individuals. Mild hypothyroidism is present in as many as 15% of older adults. Hypothyroidism is more common in women.

Hypothyroidism continues to grow significantly in the country particularly among women. A survey conducted by Indian Thyroid Society depicts one in ten adults in India suffer from hypothyroidism. According to survey, the disease is more prevalent among women who are three times more likely to be affected by hypothyroidism than men especially in the age group of 46-54 years. A significant proportion of patient population may go undetected and untreated even as it continues to impair the daily quality of life, work performance and economic productivity [14].

Thyroid hormone deficiency affects almost all body functions; and hypothyroidism if left untreated, may lead to complications such as infertility, delirium, dementia, cerebellar ataxia, seizures, psychosis (myxedema madness), confusion, myxedema coma, hypothermia, severe cardiac failure (myxedema heart), pericardial effusions, etc.

In conventional medicine, levothyroxine is being used effectively in the management of hypothyroidism, but it can suppress the TSH to subnormal range and can cause serious side effects on bone density and cardiac function, such as osteoporosis, atrial fibrillation, myocardial ischaemia, etc. Therefore, there is a need to develop safe and effective drug for the management of Qillat-e-Darqiyyat Aá¹£li (Primary Hypothyroidism).

In a recent survey conducted by American Thyroid Association demonstrated that patients taking natural preparations, rather than synthetic hormone replacement therapy or combination therapy, were more satisfied with their treatment [20]. Asgand (Withania somnifera) and Brahmi (Bacopa monnieri) have been used for centuries in Unani system of medicine for various ailments; and a combination of Asgand and Brahmi is being used for the management of depression, anxiety and chronic stress[22]; none of the studies have evaluated the effect of this drug combination in hypothyroidism. However, it has been shown in most of the pharmacological studies that both the drugs can stimulate the thyroid gland to produce more T4 hormone [15-17,19,23,24].

Keeping these facts in mind, it has been decided to conduct a research work entitled “A Randomized, Active-Controlled, Assessor-Blinded, Parallel Group Clinical Study to evaluate the safety and efficacy of Asgand and Brahmi in the Management of Qillat-e-Darqiyyat Aá¹£li (Primary Hypothyroidism)â€.

|Review of Literature

The thyroid gland is a butterfly-shaped endocrine gland that is located in the lower front of the neck. The thyroid’s job is to make thyroid hormones, which are secreted into the blood and then carried to every tissue in the body. Thyroid hormone helps the body use energy, stay warm and keep the brain, heart, muscles, and other organs working as they should. Hypothyroidism is an underactive thyroid gland [1]. Hypothyroidism means that the thyroid gland can’t make enough thyroid hormone to keep the body running normally. When thyroid hormone levels are too low, the body’s cells can’t get enough thyroid hormone and the body’s processes start slowing down and shows the symptoms like tiredness, weakness, dry skin, feeling cold, hair loss, difficulty concentrating, poor memory, constipation, weight gain with poor appetite, dyspnoea, hoarse voice, menorrhagia (later oligomenorrhoea or amenorrhoea), paraesthesia, impaired hearing; and signs like dry coarse skin, cool peripheral extremities, puffy face, hands, and feet (myxoedema), diffuse alopecia, bradycardia, peripheral edema, delayed tendon reflex relaxation, Carpal Tunnel Syndrome, and serous cavity effusions [2].

As such hypothyroidism has not been described in Unani classical literature, but some of the clinical features associated with this disease are very much similar to those described in the context of Su’-i-MizÄj BÄrid (abnormal cold temperament). According to Unani literature, the normal temperament of the thyroid gland is hot [3], but in hypothyroidism it changes from hot to abnormal cold temperament (Su’-i-MizÄj BÄrid). Some Unani scholars consider hypothyroidism as BalghmaÄ« (Phlegmatic) disease. Ghlaba-i-Balgham (domination of phlegmatic humour) is characterized by bradycardia, low volume pulse, sluggishness of skeletal muscles, puffiness, peripheral edema, cool peripheral extremities, sluggish thinking. These signs and symptoms are found in patients with hypothyroidism [4]. The signs and symptoms of Su’-i-MizÄj BÄrid (abnormal cold temperament) include Khushk wa KhurdarÄ« Jild (dry and coarse skin), Shuḥūb (skin pallor), LisÄn SamÄ«k (thick tongue), Fará¹­ al-Nawm (excessive sleep), TakÄn wa Kasalmandi (lethargy and somnolence), NabḠBaá¹­Ä« wa MutafÄwit (low volume pulse), KhafaqÄn (palpitation), Tahabbuj (puffiness of face), Kund Zahni (diminished intellectual functions), Ḍu‘f al-Shahwa (loss of libido), Ḥuá¹£r (constipation), Ḍu‘f al-IshtiḥÄ’ (decreased appetite), [5-9,18,21] etc; and these features coincides with the clinical manifestations of Qillat-e-Darqiyyat (hypothyroidism). Thus, Su’-i-MizÄj BÄrid including Su’-i-MizÄj BalghmaÄ« may beinterpreted with the clinical presentations of Qillat-e-Darqiyyat (hypothyroidism). Although the ancient Unani physicians have described a common disorder of thyroid gland in their literature as goiter (enlargement of thyroid gland) and its treatment.

BuqrÄt (Hippocrates) (460-337 BC) narrated in context to the glands that “when glands of the neck become diseased themselves, they become tubercular and produce strumaâ€. The term “struma†is still used in some European countries (e.g. Austria, Italy) as the medical designation of goiter.

IsmÄ‘il JurjÄnī’s ’Treasure of Medicine’ first associated with exophthalmos (protrusion of the eyes), we now associate it with Grave’s disease (goiter). ‘AlÄ« ibn ‘AbbÄs MajÅ«sÄ« (d. 994 AD) stated that the Waram which occurs due to Balgham-e-GhalÄ«z results in Ghayngha (goiter) which are similar to glands. Ibn Hubal BaghdÄdÄ« (1121-1213 AD) mentioned exophthalmic goiter under the heading Juḥūẓ al-‘Ayn (exophthalmos) in his book, “KitÄb al-MukhtÄrÄt fi’l Ṭibbâ€. He narrated as: “The main cause of Juḥūẓ al-‘Ayn is accumulation of matter. The matter may be liquid or gaseous in nature. These matters accumulate in the vessels of the eyes result in dilatation of the vessels. Collectively we can say that increased pressure of vessels of eyes is the cause of diseaseâ€.

According to Ibn SÄ«nÄ (Avicenna), the signs of phlegm being predominant are excessive pallor, flabbiness of body, cold and moist skin, excessive salivation and viscid saliva. Thirst is diminished especially in elderly persons except of course when the acid phlegm predominates. A weak digestion with acid eructation, pale urine, excessive sleepiness, flabby muscles, mental dullness and a soft pulse of slow rate and speed are characteristics of this condition. According to this, the line of treatment when a temperamental abnormality is simple, i.e., without any complicating factor, its treatment is counteraction [7].