K4 Elite
K4 Elite
DSIP is a nonapeptide isolated from rabbit cerebral venous blood in 1977. Human interventional studies were conducted mainly between 1981 and 1992, almost all using slow intravenous infusion of synthetic DSIP at 25-30 nmol/kg, in small groups of healthy volunteers, chronic insomniacs, patients with chronic pain, and inpatients in alcohol or opiate withdrawal. Results were mixed: Schneider-Helmert's group reported sleep normalisation, whereas two later double-blind studies (Monti 1987; Bes 1992) found little or no clinically meaningful effect. A 2009 anaesthesia study is the only modern human trial. All evidence is old, small, and predates current trial-reporting standards.
Each row records what a published study did: who it enrolled, the regimen it administered to those subjects, and what it reported. These are historical study descriptions, not protocols to follow.
| Study | Population | Regimen as reported | Primary findings |
|---|---|---|---|
| Schneider-Helmert et al., Int J Clin Pharmacol Ther Toxicol 1981 (double-blind crossover; first human study) | 6 healthy volunteers (4 men, 2 women) | Volunteers received synthetic DSIP 25 nmol/kg or placebo as a slow intravenous infusion in the morning. | Median total sleep time within 130 minutes after infusion increased by 59% versus placebo, with shorter sleep onset and better efficiency the following night; no psychological, physiological or biochemical side effects were observed. |
| Schneider-Helmert & Schoenenberger, Experientia 1981 | 6 middle-aged chronic insomniacs | Patients received a single acute intravenous dose of synthetic DSIP 25 nmol/kg. | Longer sleep duration and fewer interruptions were recorded, with sleep-promoting effects emerging in the second hour after injection; no daytime sedation or other side effects were reported. |
| Schneider-Helmert, Neuropsychobiology 1986 | 18 chronic psychophysiological insomniacs (middle-aged 29-59 y and older 60-83 y) | Patients received DSIP 30 nmol/kg intravenously on six occasions over one week, followed by a one-week follow-up. | Sleep measures reached normal values by the end of administration in middle-aged patients and by the end of follow-up in elderly patients; effect size correlated with baseline severity. |
| Schneider-Helmert, Neuropsychobiology 1987 (placebo-controlled, double-blind) | 14 middle-aged patients with severe chronic insomnia | Patients received DSIP under placebo-controlled, double-blind conditions for 7 successive nights, with polysomnography at baseline, during treatment and one post-treatment placebo night. | Night sleep improved with the first and repeated doses, effects persisted into the first post-treatment night, and daytime alertness and performance scores increased. |
| Monti et al., Int J Clin Pharmacol Res 1987 (double-blind crossover) | Chronic insomniac patients | Patients received DSIP 25 nmol/kg or placebo intravenously during four nights in a double-blind crossover design. | Awakenings and waking time decreased and total/NREM sleep time increased under DSIP, but differences from baseline or placebo were not significant or already present at baseline; the authors concluded the improvement was of little clinical significance. |
| Bes et al., Neuropsychobiology 1992 (double-blind, matched-pairs parallel groups) | 16 chronic insomniac patients | Half of the patients received DSIP 25 nmol/kg intravenously and half glucose placebo in the afternoon before three consecutive laboratory nights. | Sleep efficiency was higher and sleep latency shorter with DSIP, but the effects were weak, partly attributable to change in the placebo group, and subjective sleep quality did not change; the authors concluded short-term DSIP was unlikely to be of major therapeutic benefit. |
| Dick et al., Eur Neurol 1984 (open inpatient series; withdrawal syndromes) | 107 inpatients with alcohol (n=47) or opiate (n=60) withdrawal symptoms | Patients received DSIP intravenously as the sole treatment for withdrawal; opiate-dependent patients required more injections than alcohol-dependent patients. | Clinical withdrawal signs were reported to disappear or improve markedly in 97% of evaluable opiate and 87% of alcohol patients, with anxiety resolving more slowly; tolerance was described as good apart from headaches in a few patients. |
| Dick, Grandjean & Tissot, Neuropsychobiology 1983 (open series) | 67 patients with withdrawal symptoms (28 alcohol, 39 opiate); 49 evaluable | Patients received DSIP 25 nmol/kg intravenously as sole treatment. | A beneficial effect on somatic withdrawal signs was reported in 48 of 49 evaluable patients, with anxiety resolving over hours; no major side effect occurred. |
| Larbig et al., Eur Neurol 1984 (open pilot; chronic pain) | 7 patients with migraine/vasomotor headache, chronic tinnitus or psychogenic pain | Patients received DSIP intravenously on 5 consecutive days followed by 5 further injections at 48-72-hour intervals. | Pain ratings fell significantly in 6 of 7 patients versus the baseline period, with a concurrent reduction in depressive symptoms. |
| Bjartell et al., Psychoneuroendocrinology 1989 (randomized double-blind crossover) | 11 healthy men aged 25-39 | Volunteers received a single intravenous dose of synthetic DSIP 25 nmol/kg or saline. | Plasma ACTH-like immunoreactivity was reduced for at least 3 hours after DSIP while cortisol was unchanged. |
| Pomfrett et al., Eur J Anaesthesiol 2009 (randomized, saline-controlled) | 24 female ASA I-II surgical patients (12 saline controls) | Patients received an intravenous bolus of DSIP (Clinalfa) at 25, 50 or 100 nmol/kg, once awake and again after propofol induction during isoflurane maintenance. | DSIP increased heart rate, decreased heart-rate variability and, paradoxically, reduced EEG delta rhythm and increased bispectral index at 25 nmol/kg during isoflurane anaesthesia. |
Effects recorded in the cited reports. Frequencies are those the source reported, in the population that source studied.
| Effect | Frequency / context | Source |
|---|---|---|
| Headache | Reported by 'a few patients' among 107 inpatients treated for alcohol/opiate withdrawal (Dick 1984); exact frequency not given. | DSIP in the treatment of withdrawal syndromes from alcohol and opiates ↗ |
| Heart-rate increase and reduced heart-rate variability | Observed in anaesthetised surgical patients after intravenous bolus 25-100 nmol/kg (Pomfrett 2009, n=12 treated). | Delta sleep-inducing peptide alters bispectral index, the electroencephalogram and heart rate variability when used as an adjunct to isoflurane anaesthesia ↗ |
| Transient arousal in the first hour after injection | A slight arousing effect preceded sleep promotion in 6 chronic insomniacs given 25 nmol/kg IV (Schneider-Helmert 1981). | The influence of synthetic DSIP (delta-sleep-inducing-peptide) on disturbed human sleep ↗ |
| No side effects reported | 6 healthy volunteers (Schneider-Helmert 1981) and 49 evaluable withdrawal patients (Dick 1983) had no reported side effects; the 1983 overview noted that slow injection 'proved essential'. | Effects of DSIP in man. Multifunctional psychophysiological properties besides induction of natural sleep ↗ |
Interactions documented in trial reports, prescribing information or pharmacology references.
| Agent | Type | Note | Source |
|---|---|---|---|
| Isoflurane/propofol anaesthesia | pharmacodynamic | DSIP altered depth-of-anaesthesia indices (reduced delta power, increased BIS, reduced burst suppression) when given during isoflurane anaesthesia (Pomfrett 2009). | Delta sleep-inducing peptide alters bispectral index, the electroencephalogram and heart rate variability when used as an adjunct to isoflurane anaesthesia ↗ |
No contraindications with a verifiable citation have been indexed for this compound.